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Potential Anti-SARS-CoV-2 Molecular Strategies
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Potential Anti-SARS-CoV-2 Molecular Strategies

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 56149

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Giovanni N. Roviello

E-Mail Website
Guest Editor
Institute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Via P. Castellino 111, 80131 Naples, Italy
Interests: bioinorganic chemistry; synthetic chemistry; nucleic acid chemistry; spectroscopic studies; computational studies; environmental chemistry
Special Issues, Collections and Topics in MDPI journals
Dr. Caterina Vicidomini

E-Mail Website
Guest Editor
Istituto di Biostrutture e Bioimmagini IBB-CNR, Via Tommaso De Amicis 95, 80145 Naples, Italy
Interests: pharmaceutical chemistry; neurodrugs; protein interactions; spectroscopy; computational chemistry; phytochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic, associated with the new virus SARS-CoV-2, has globally attracted the attention of the scientific community to the theme of coronaviruses (CoVs) and the prophylaxis and therapy of infections caused by the most pathogenic members of this family. In fact, while most CoVs are usually associated with mild symptoms such as those of the seasonal “common cold”, three CoVs have emerged in recent decades that can lead to severe pneumonia and in some cases death: SARS-CoV-1 (which caused SARS about 18 years ago), MERS-CoV (causing the highly fatal MERS in Middle East countries), and SARS-CoV-2 (associated with COVID-19). It is believed that CoVs are of zoonotic origin, and highly pathogenic members of their family could periodically emerge, leading to sanitary and consequent socio-economic impacts. Therefore, research on CoVs should be strengthened and encouraged even after, hopefully soon, the current pandemic is over.

In this Special Issue, we wish to focus on the area of novel anti-coronavirus drug discovery, design, and development, with the main interest, obviously, on the most pathogenic CoVs and in particular SARS-CoV-2 and MERS-CoV. However, contributions on other CoVs are also welcome as they could improve overall knowledge on the Coronaviridae. Other themes of interest are inherent in the development of vaccines against CoVs, and the investigation of the biomolecular processes targetable by anti-CoV strategies.

The issue is open to the submission of both original articles and reviews that describe research and ideas on themes around anti-CoV molecular strategies.

Dr. Giovanni N. Roviello
Dr. Caterina Vicidomini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Coronavirus
  • SARS-CoV-2
  • MERS-CoV
  • COVID-19
  • Antiviral drugs
  • Vaccines
  • Biomolecular targets
  • RdRp
  • Mpro
  • Spike protein
  • Anti-COVID-19 strategies
  • Drug repurposing
  • Natural products
  • Synthetic antivirals

Published Papers (15 papers)

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Editorial

Jump to: Research, Review

5 pages, 408 KiB  
Editorial
Potential Anti-SARS-CoV-2 Molecular Strategies
by Caterina Vicidomini and Giovanni N. Roviello
Molecules 2023, 28(5), 2118; https://doi.org/10.3390/molecules28052118 - 24 Feb 2023
Cited by 2 | Viewed by 1330
Abstract
Finding effective antiviral molecular strategies was a main concern in the scientific community when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 as an easily transmissible and potentially deadly β-coronavirus able to cause the coronavirus disease 19 [...] Read more.
Finding effective antiviral molecular strategies was a main concern in the scientific community when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 as an easily transmissible and potentially deadly β-coronavirus able to cause the coronavirus disease 19 (COVID-19), which famously led to one of the most worrying pandemics in recent times. Other members of this zoonotic pathogenic family were already known before 2019, but apart from the SARS-CoV, which was responsible of severe acute respiratory syndrome (SARS) pandemic in 2002/2003, and Middle East respiratory syndrome coronavirus (MERS-CoV), whose main impact on humans is geographically restricted to Middle Eastern countries, the other human β-coronaviruses known at that time were those typically associated with common cold symptoms which had not led to the development of any specific prophylactic or therapeutic measures. Although SARS-CoV-2 and its mutations are still causing illness in our communities, COVID-19 is less deadly than before and we are returning to normality. Overall, the main lesson learnt after the past few years of pandemic is that keeping our bodies healthy and immunity defenses strong using sport, nature-inspired measures, and using functional foods are powerful weapons for preventing the more severe forms of illness caused by SARS-CoV-2 and, from a more molecular perspective, that finding drugs with mechanisms of action involving biological targets conserved within the different mutations of SARS-CoV-2—and possibly within the entire family of β-coronaviruses—gives more therapeutic opportunities in the scenario of future pandemics based on these pathogens. In this regard, the main protease (Mpro), having no human homologues, offers a lower risk of off-target reactivity and represents a suitable therapeutic target in the search for efficacious, broad-spectrum anti-β-coronavirus drugs. Herein, we discuss on the above points and also report some molecular approaches presented in the past few years to counteract the effects of β-coronaviruses, with a special focus on SARS-CoV-2 but also MERS-CoV. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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Research

Jump to: Editorial, Review

21 pages, 6189 KiB  
Article
Neuropeptides, New Ligands of SARS-CoV-2 Nucleoprotein, a Potential Link between Replication, Inflammation and Neurotransmission
by Julien Henri, Laetitia Minder, Kevin Mohanasundaram, Sébastien Dilly, Anne Goupil-Lamy, Carmelo Di Primo and Anny Slama Schwok
Molecules 2022, 27(22), 8094; https://doi.org/10.3390/molecules27228094 - 21 Nov 2022
Cited by 2 | Viewed by 2244
Abstract
This work identifies new ligands of the nucleoprotein N of SARS-CoV-2 by in silico screening, which used a new model of N, built from an Alphafold model refined by molecular dynamic simulations. The ligands were neuropeptides, such as substance P (1-7) and enkephalin, [...] Read more.
This work identifies new ligands of the nucleoprotein N of SARS-CoV-2 by in silico screening, which used a new model of N, built from an Alphafold model refined by molecular dynamic simulations. The ligands were neuropeptides, such as substance P (1-7) and enkephalin, bound at a large site of the C-terminal or associated with the N-terminal β−sheet. The BA4 and BA5 Omicron variants of N also exhibited a large site as in wt N, and an increased flexibility of the BA5 variant, enabling substance P binding. The binding sites of some ligands deduced from modeling in wt N were assessed by mutation studies in surface plasmon resonance experiments. Dynamic light scattering showed that the ligands impeded RNA binding to N, which likely inhibited replication. We suggest that the physiological role of these neuropeptides in neurotransmission, pain and vasodilation for cholecystokinin and substance P could be altered by binding to N. We speculate that N may link between viral replication and multiple pathways leading to long COVID-19 symptoms. Therefore, N may constitute a “danger hub” that needs to be inhibited, even at high cost for the host. Antivirals targeted to N may therefore reduce the risk of brain fog and stroke, and improve patients’ health. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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10 pages, 2467 KiB  
Communication
Effects of a Shift of the Signal Peptide Cleavage Site in Signal Peptide Variant on the Synthesis and Secretion of SARS-CoV-2 Spike Protein
by Zhikai Zhang, Xuan Wan, Xinyue Li and Chengsong Wan
Molecules 2022, 27(19), 6688; https://doi.org/10.3390/molecules27196688 - 08 Oct 2022
Cited by 3 | Viewed by 1845
Abstract
The COVID-19 pandemic is caused by SARS-CoV-2; the spike protein is a key structural protein that mediates infection of the host by SARS-CoV-2. In this study, we aimed to evaluate the effects of signal peptide on the secretion and release of SARS-CoV-2 spike [...] Read more.
The COVID-19 pandemic is caused by SARS-CoV-2; the spike protein is a key structural protein that mediates infection of the host by SARS-CoV-2. In this study, we aimed to evaluate the effects of signal peptide on the secretion and release of SARS-CoV-2 spike protein. Therefore, we constructed a signal peptide deletion mutant and three signal peptide site-directed mutants. The (H) region and (C) region in the signal peptide of L5F-S13I mutant have changed significantly, compared with wild type, L5F and S13I. We demonstrated the effects of signal peptide on the secretion and synthesis of RBD protein, finding that mutation of S13 to I13 on the signal peptide is more conducive to the secretion of RBD protein, which was mainly due to the shift of the signal peptide cleavage site in the mutant S13I. Here, we not only investigated the structure of the N-terminal signal peptide of the SARS-CoV-2 spike protein but also considered possible secretory pathways. We suggest that the development of drugs that target the signal peptide of the SARS-CoV-2 spike protein may have potential to treat COVID-19 in the future. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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22 pages, 7283 KiB  
Article
In Silico Study towards Repositioning of FDA-Approved Drug Candidates for Anticoronaviral Therapy: Molecular Docking, Molecular Dynamics and Binding Free Energy Calculations
by Wesam S. Qayed, Rafaela S. Ferreira and José Rogério A. Silva
Molecules 2022, 27(18), 5988; https://doi.org/10.3390/molecules27185988 - 14 Sep 2022
Cited by 11 | Viewed by 2551
Abstract
The SARS-CoV-2 targets were evaluated for a set of FDA-approved drugs using a combination of drug repositioning and rigorous computational modeling methodologies such as molecular docking and molecular dynamics (MD) simulations followed by binding free energy calculations. Six FDA-approved drugs including, Ouabain, Digitoxin, [...] Read more.
The SARS-CoV-2 targets were evaluated for a set of FDA-approved drugs using a combination of drug repositioning and rigorous computational modeling methodologies such as molecular docking and molecular dynamics (MD) simulations followed by binding free energy calculations. Six FDA-approved drugs including, Ouabain, Digitoxin, Digoxin, Proscillaridin, Salinomycin and Niclosamide with promising anti-SARS-CoV-2 activity were screened in silico against four SARS-CoV-2 proteins—papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), SARS-CoV-2 main protease (Mpro), and adaptor-associated kinase 1 (AAK1)—in an attempt to define their promising targets. The applied computational techniques suggest that all the tested drugs exhibited excellent binding patterns with higher scores and stable complexes compared to the native protein cocrystallized inhibitors. Ouabain was suggested to act as a dual inhibitor for both PLpro and Mpro enzymes, while Digitoxin bonded perfectly to RdRp. In addition, Salinomycin targeted PLpro. Particularly, Niclosamide was found to target AAK1 with greater affinity compared to the reference drug. Our study provides comprehensive molecular-level insights for identifying or designing novel anti-COVID-19 drugs. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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Graphical abstract

20 pages, 4695 KiB  
Article
Transcriptomics, Cheminformatics, and Systems Pharmacology Strategies Unveil the Potential Bioactives to Combat COVID-19
by Sivakumar Adarshan, Sakthivel Akassh, Krishnakumar Avinash, Mathivanan Bharathkumar, Pandiyan Muthuramalingam, Hyunsuk Shin, Venkidasamy Baskar, Jen-Tsung Chen, Veluswamy Bhuvaneshwari and Manikandan Ramesh
Molecules 2022, 27(18), 5955; https://doi.org/10.3390/molecules27185955 - 13 Sep 2022
Cited by 5 | Viewed by 2052
Abstract
Coronavirus disease (COVID-19) is a viral disease caused by the SARS-CoV-2 virus and is becoming a global threat again because of the higher transmission rate and lack of proper therapeutics as well as the rapid mutations in the genetic pattern of SARS-CoV-2. Despite [...] Read more.
Coronavirus disease (COVID-19) is a viral disease caused by the SARS-CoV-2 virus and is becoming a global threat again because of the higher transmission rate and lack of proper therapeutics as well as the rapid mutations in the genetic pattern of SARS-CoV-2. Despite vaccinations, the prevalence and recurrence of this infection are still on the rise, which urges the identification of potential global therapeutics for a complete cure. Plant-based alternative medicine is becoming popular worldwide because of its higher efficiency and minimal side effects. Yet, identifying the potential medicinal plants and formulating a plant-based medicine is still a bottleneck. Hence, in this study, the systems pharmacology, transcriptomics, and cheminformatics approaches were employed to uncover the multi-targeted mechanisms and to screen the potential phytocompounds from significant medicinal plants to treat COVID-19. These approaches have identified 30 unique COVID-19 human immune genes targeted by the 25 phytocompounds present in four selected ethnobotanical plants. Differential and co-expression profiling and pathway enrichment analyses delineate the molecular signaling and immune functional regulations of the COVID-19 unique genes. In addition, the credibility of these compounds was analyzed by the pharmacological features. The current holistic finding is the first to explore whether the identified potential bioactives could reform into a drug candidate to treat COVID-19. Furthermore, the molecular docking analysis was employed to identify the important bioactive compounds; thus, an ultimately significant medicinal plant was also determined. However, further laboratory evaluation and clinical validation are required to determine the efficiency of a therapeutic formulation against COVID-19. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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17 pages, 3527 KiB  
Article
Correlates with Vaccine Protective Capacity and COVID-19 Disease Symptoms Identified by Serum Proteomics in Vaccinated Individuals
by Margarita Villar, José Miguel Urra, Sara Artigas-Jerónimo, Lorena Mazuecos, Marinela Contreras, Rita Vaz-Rodrigues, Francisco J. Rodríguez-del-Río, Christian Gortázar and José de la Fuente
Molecules 2022, 27(18), 5933; https://doi.org/10.3390/molecules27185933 - 13 Sep 2022
Cited by 3 | Viewed by 1940
Abstract
In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, [...] Read more.
In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, genetic virus variants are still circulating among vaccinated individuals with different disease symptomatology. Understanding the protective- or disease-associated mechanisms in vaccinated individuals is relevant to advances in vaccine development and implementation. To address this objective, serum-protein profiles were characterized by quantitative proteomics and data-analysis algorithms in four cohorts of uninfected and SARS-CoV-2-infected vaccinated individuals with asymptomatic, non-severe, and severe disease symptomatology. The results show that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective- or disease-associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In non-severe cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins, including the spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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Graphical abstract

15 pages, 3237 KiB  
Article
In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease
by Vishma Pratap Sur, Madhab Kumar Sen and Katerina Komrskova
Molecules 2021, 26(20), 6199; https://doi.org/10.3390/molecules26206199 - 14 Oct 2021
Cited by 9 | Viewed by 2930
Abstract
The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, [...] Read more.
The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (Mpro). The SARS-CoV-2 main protease (Mpro) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM, and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (Mpro) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and through molecular dynamic (MD) simulation their stability, interaction, and conformation were analyzed. In summary, this study identified the most suitable compounds for targeting Mpro, and we recommend using these compounds as potential drug molecules against SARS-CoV-2 after follow up studies. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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Graphical abstract

18 pages, 9006 KiB  
Article
In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10
by Ibrahim H. Eissa, Mohamed M. Khalifa, Eslam B. Elkaeed, Elsayed E. Hafez, Aisha A. Alsfouk and Ahmed M. Metwaly
Molecules 2021, 26(20), 6151; https://doi.org/10.3390/molecules26206151 - 12 Oct 2021
Cited by 45 | Viewed by 2495
Abstract
In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The applied selection methods aimed to pick the most relevant inhibitor of SARS-CoV-2 nsp10. At first, a structural similarity study [...] Read more.
In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The applied selection methods aimed to pick the most relevant inhibitor of SARS-CoV-2 nsp10. At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. The similarity analysis culled 30 candidates. Secondly, a fingerprint study against SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. The docking studies picked 48, 182, 220, 221, and 284. While the ADMET analysis expected the likeness of the five candidates to be drugs, the toxicity study preferred compounds 48 and 182. Finally, a density-functional theory (DFT) study suggested vidarabine (182) to be the most relevant SARS-Cov-2 nsp10 inhibitor. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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9 pages, 7518 KiB  
Communication
Inactivation Activities of Ozonated Water, Slightly Acidic Electrolyzed Water and Ethanol against SARS-CoV-2
by Yohei Takeda, Dulamjav Jamsransuren, Yoshimasa Makita, Akihiro Kaneko, Sachiko Matsuda, Haruko Ogawa and Hourei Oh
Molecules 2021, 26(18), 5465; https://doi.org/10.3390/molecules26185465 - 08 Sep 2021
Cited by 12 | Viewed by 2706
Abstract
This study aimed to compare the SARS-CoV-2-inactivation activity and virucidal mechanisms of ozonated water (OW) with those of slightly acidic electrolyzed water (SAEW) and 70% ethanol (EtOH). SARS-CoV-2-inactivation activity was evaluated in a virus solution containing 1%, 20% or 40% fetal bovine serum [...] Read more.
This study aimed to compare the SARS-CoV-2-inactivation activity and virucidal mechanisms of ozonated water (OW) with those of slightly acidic electrolyzed water (SAEW) and 70% ethanol (EtOH). SARS-CoV-2-inactivation activity was evaluated in a virus solution containing 1%, 20% or 40% fetal bovine serum (FBS) with OW, SAEW or EtOH at a virus-to-test solution ratio of 1:9, 1:19 or 1:99 for a reaction time of 20 s. EtOH showed the strongest virucidal activity, followed by SAEW and OW. Even though EtOH potently inactivated the virus despite the 40% FBS concentration, virus inactivation by OW and SAEW decreased in proportion to the increase in FBS concentration. Nevertheless, OW and SAEW showed potent virucidal activity with 40% FBS at a virus-to-test solution ratio of 1:99. Real-time PCR targeting the viral genome revealed that cycle threshold values in the OW and SAEW groups were significantly higher than those in the control group, suggesting that OW and SAEW disrupted the viral genome. Western blotting analysis targeting the recombinant viral spike protein S1 subunit showed a change in the specific band into a ladder upon treatment with OW and SAEW. OW and SAEW may cause conformational changes in the S1 subunit of the SARS-CoV-2 spike protein. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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Graphical abstract

25 pages, 5889 KiB  
Article
Pharmacophore-Based Virtual Screening, Quantum Mechanics Calculations, and Molecular Dynamics Simulation Approaches Identified Potential Natural Antiviral Drug Candidates against MERS-CoV S1-NTD
by Thamer A. Bouback, Sushil Pokhrel, Abdulaziz Albeshri, Amal Mohammed Aljohani, Abdus Samad, Rahat Alam, Md Saddam Hossen, Khalid Al-Ghamdi, Md. Enamul Kabir Talukder, Foysal Ahammad, Ishtiaq Qadri and Jesus Simal-Gandara
Molecules 2021, 26(16), 4961; https://doi.org/10.3390/molecules26164961 - 17 Aug 2021
Cited by 34 | Viewed by 6421
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The [...] Read more.
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The N-terminal domain (NTD) of receptor-binding S1 subunit of coronavirus spike (S) proteins can recognize a variety of host protein and mediates entry into human host cells. Blocking the entry by targeting the S1-NTD of the virus can facilitate the development of effective antiviral drug candidates against the pathogen. Therefore, the study has been designed to identify effective antiviral drug candidates against the MERS-CoV by targeting S1-NTD. Initially, a structure-based pharmacophore model (SBPM) to the active site (AS) cavity of the S1-NTD has been generated, followed by pharmacophore-based virtual screening of 11,295 natural compounds. Hits generated through the pharmacophore-based virtual screening have re-ranked by molecular docking and further evaluated through the ADMET properties. The compounds with the best ADME and toxicity properties have been retrieved, and a quantum mechanical (QM) based density-functional theory (DFT) has been performed to optimize the geometry of the selected compounds. Three optimized natural compounds, namely Taiwanhomoflavone B (Amb23604132), 2,3-Dihydrohinokiflavone (Amb23604659), and Sophoricoside (Amb1153724), have exhibited substantial docking energy >−9.00 kcal/mol, where analysis of frontier molecular orbital (FMO) theory found the low chemical reactivity correspondence to the bioactivity of the compounds. Molecular dynamics (MD) simulation confirmed the stability of the selected natural compound to the binding site of the protein. Additionally, molecular mechanics generalized born surface area (MM/GBSA) predicted the good value of binding free energies (ΔG bind) of the compounds to the desired protein. Convincingly, all the results support the potentiality of the selected compounds as natural antiviral candidates against the MERS-CoV S1-NTD. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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11 pages, 1666 KiB  
Article
Severe Acute Respiratory Syndrome Coronavirus-2 Inactivation Activity of the Polyphenol-Rich Tea Leaf Extract with Concentrated Theaflavins and Other Virucidal Catechins
by Yohei Takeda, Kyohei Tamura, Dulamjav Jamsransuren, Sachiko Matsuda and Haruko Ogawa
Molecules 2021, 26(16), 4803; https://doi.org/10.3390/molecules26164803 - 08 Aug 2021
Cited by 6 | Viewed by 2741
Abstract
Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is producing a large number of infections and deaths globally, the development of supportive and auxiliary treatments is attracting increasing attention. Here, we evaluated SARS-CoV-2-inactivation activity of the polyphenol-rich tea leaf extract TY-1 containing concentrated [...] Read more.
Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is producing a large number of infections and deaths globally, the development of supportive and auxiliary treatments is attracting increasing attention. Here, we evaluated SARS-CoV-2-inactivation activity of the polyphenol-rich tea leaf extract TY-1 containing concentrated theaflavins and other virucidal catechins. The TY-1 was mixed with SARS-CoV-2 solution, and its virucidal activity was evaluated. To evaluate the inhibition activity of TY-1 in SARS-CoV-2 infection, TY-1 was co-added with SARS-CoV-2 into cell culture media. After 1 h of incubation, the cell culture medium was replaced, and the cells were further incubated in the absence of TY-1. The viral titers were then evaluated. To evaluate the impacts of TY-1 on viral proteins and genome, TY-1-treated SARS-CoV-2 structural proteins and viral RNA were analyzed using western blotting and real-time RT-PCR, respectively. TY-1 showed time- and concentration-dependent virucidal activity. TY-1 inhibited SARS-CoV-2 infection of cells. The results of western blotting and real-time RT-PCR suggested that TY-1 induced structural change in the S2 subunit of the S protein and viral genome destruction, respectively. Our findings provided basic insights in vitro into the possible value of TY-1 as a virucidal agent, which could enhance the current SARS-CoV-2 control measures. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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Review

Jump to: Editorial, Research

14 pages, 653 KiB  
Review
Strategies Tackling Viral Replication and Inflammatory Pathways as Early Pharmacological Treatment for SARS-CoV-2 Infection: Any Potential Role for Ketoprofen Lysine Salt?
by Domenica Francesca Mariniello, Valentino Allocca, Vito D’Agnano, Riccardo Villaro, Luigi Lanata, Michela Bagnasco, Luigi Aronne, Andrea Bianco and Fabio Perrotta
Molecules 2022, 27(24), 8919; https://doi.org/10.3390/molecules27248919 - 15 Dec 2022
Cited by 3 | Viewed by 1847
Abstract
COVID-19 is an infective disease resulting in widespread respiratory and non-respiratory symptoms prompted by SARS-CoV-2 infection. Interaction between SARS-CoV-2 and host cell receptors prompts activation of pro-inflammatory pathways which are involved in epithelial and endothelial damage mechanisms even after viral clearance. Since inflammation [...] Read more.
COVID-19 is an infective disease resulting in widespread respiratory and non-respiratory symptoms prompted by SARS-CoV-2 infection. Interaction between SARS-CoV-2 and host cell receptors prompts activation of pro-inflammatory pathways which are involved in epithelial and endothelial damage mechanisms even after viral clearance. Since inflammation has been recognized as a critical step in COVID-19, anti-inflammatory therapies, including both steroids and non-steroids as well as cytokine inhibitors, have been proposed. Early treatment of COVID-19 has the potential to affect the clinical course of the disease regardless of underlying comorbid conditions. Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for symptomatic relief of upper airway infections, became the mainstay of early phase treatment of COVID-19. In this review, we discuss the current evidence for using NSAIDs in early phases of SARS-CoV-2 infection with focus on ketoprofen lysine salt based on its pharmacodynamic and pharmacokinetic features. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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17 pages, 1411 KiB  
Review
Catechins: Therapeutic Perspectives in COVID-19-Associated Acute Kidney Injury
by Lúcio Ricardo Leite Diniz, Hatem A. Elshabrawy, Marilia Trindade de Santana Souza, Allana Brunna Sucupira Duarte, Sabarno Datta and Damião Pergentino de Sousa
Molecules 2021, 26(19), 5951; https://doi.org/10.3390/molecules26195951 - 30 Sep 2021
Cited by 9 | Viewed by 2783
Abstract
Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute [...] Read more.
Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5–46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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17 pages, 633 KiB  
Review
An Update on COVID-19 Vaccine Induced Thrombotic Thrombocytopenia Syndrome and Some Management Recommendations
by Amin Islam, Mohammed Sheraz Bashir, Kevin Joyce, Harunor Rashid, Ismail Laher and Shereen Elshazly
Molecules 2021, 26(16), 5004; https://doi.org/10.3390/molecules26165004 - 18 Aug 2021
Cited by 22 | Viewed by 7315
Abstract
The thrombotic thrombocytopenia syndrome (TTS), a complication of COVID-19 vaccines, involves thrombosis (often cerebral venous sinus thrombosis) and thrombocytopenia with occasional pulmonary embolism and arterial ischemia. TTS appears to mostly affect females aged between 20 and 50 years old, with no predisposing risk [...] Read more.
The thrombotic thrombocytopenia syndrome (TTS), a complication of COVID-19 vaccines, involves thrombosis (often cerebral venous sinus thrombosis) and thrombocytopenia with occasional pulmonary embolism and arterial ischemia. TTS appears to mostly affect females aged between 20 and 50 years old, with no predisposing risk factors conclusively identified so far. Cases are characterized by thrombocytopenia, higher levels of D-dimers than commonly observed in venous thromboembolic events, inexplicably low fibrinogen levels and worsening thrombosis. Hyper fibrinolysis associated with bleeding can also occur. Antibodies that bind platelet factor 4, similar to those associated with heparin-induced thrombocytopenia, have also been identified but in the absence of patient exposure to heparin treatment. A number of countries have now suspended the use of adenovirus-vectored vaccines for younger individuals. The prevailing opinion of most experts is that the risk of developing COVID-19 disease, including thrombosis, far exceeds the extremely low risk of TTS associated with highly efficacious vaccines. Mass vaccination should continue but with caution. Vaccines that are more likely to cause TTS (e.g., Vaxzevria manufactured by AstraZeneca) should be avoided in younger patients for whom an alternative vaccine is available. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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12 pages, 710 KiB  
Review
Molecular Basis of the Therapeutical Potential of Clove (Syzygium aromaticum L.) and Clues to Its Anti-COVID-19 Utility
by Caterina Vicidomini, Valentina Roviello and Giovanni N. Roviello
Molecules 2021, 26(7), 1880; https://doi.org/10.3390/molecules26071880 - 26 Mar 2021
Cited by 79 | Viewed by 12974
Abstract
The current COronaVIrus Disease 19 (COVID-19) pandemic caused by SARS-CoV-2 infection is enormously affecting the worldwide health and economy. In the wait for an effective global immunization, the development of a specific therapeutic protocol to treat COVID-19 patients is clearly necessary as a [...] Read more.
The current COronaVIrus Disease 19 (COVID-19) pandemic caused by SARS-CoV-2 infection is enormously affecting the worldwide health and economy. In the wait for an effective global immunization, the development of a specific therapeutic protocol to treat COVID-19 patients is clearly necessary as a short-term solution of the problem. Drug repurposing and herbal medicine represent two of the most explored strategies for an anti-COVID-19 drug discovery. Clove (Syzygium aromaticum L.) is a well-known culinary spice that has been used for centuries in folk medicine in many disorders. Interestingly, traditional medicines have used clove since ancient times to treat respiratory ailments, whilst clove ingredients show antiviral and anti-inflammatory properties. Other interesting features are the clove antithrombotic, immunostimulatory, and antibacterial effects. Thus, in this review, we discuss the potential role of clove in the frame of anti-COVID-19 therapy, focusing on the antiviral, anti-inflammatory, and antithrombotic effects of clove and its molecular constituents described in the scientific literature. Full article
(This article belongs to the Special Issue Potential Anti-SARS-CoV-2 Molecular Strategies)
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