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Biomedicines
Special Issues
Drug Development for COVID-19
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Drug Development for COVID-19

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 22403

Special Issue Editor

Dr. Yuguang Zhao

E-Mail Website
Guest Editor
The Wellcome Centre for Human Genetics, Oxford, UK
Interests: wnt signalling; viruses and receptors; drug development

Special Issue Information

Dear Colleagues,

The recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to human health and the global economy. Vaccination can significantly reduce the severe cases and death rate; however, effective therapeutics for COVID-19 are urgently needed, especially in the context of rapid virus evolution. Neutralising antibodies can be useful with high cost. Repurposed small molecule drugs like remdesivir and dexamethasone could have modest effects in moderate to severe cases. The development of effective virus-specific small molecules drugs remains a challenge, despite a lot of progress being made. Viral protease, RNA polymerase and spike proteins provide good targets for drug development. Host response modulators are also important for disease treatment. With high-throughput assays, an ample amount of high resolution structures and modern computer-aided drug design, rapid progress can be made.

Dr. Yuguang Zhao
Guest Editor

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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • vaccine
  • antibodies, nanobodies and other macromolecules
  • drug repurposing
  • virla protease inhibitors
  • viral RNA polymerase inhibitors
  • spike/RBD interacting molecules
  • host response modulators

Published Papers (4 papers)

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Research

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14 pages, 3032 KiB  
Article
OM-85 Broncho-Vaxom®, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells
by Lei Fang, Liang Zhou, Michael Tamm and Michael Roth
Biomedicines 2021, 9(11), 1544; https://doi.org/10.3390/biomedicines9111544 - 26 Oct 2021
Cited by 12 | Viewed by 10532
Abstract
In clinical studies, OM-85 Broncho-Vaxom®, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 [...] Read more.
In clinical studies, OM-85 Broncho-Vaxom®, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 on the expression of S-protein binding proteins by human bronchial epithelial cells. Human bronchial epithelial cells were treated with OM-85 over 5 days. The expression of SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2), transmembrane protease serine subtype 2 (TMPRSS2), dipeptidyl peptidase-4 (DPP4), and a disintegrin and metalloprotease 17 (ADAM17) were determined by Western blotting and quantitative RT-PCR. Soluble (s)ACE2, heparan sulfate, heparanase, and hyaluronic acid were assessed by ELISA. OM-85 significantly reduced the expression of ACE2 (p < 0.001), TMPRSS2 (p < 0.001), DPP4 (p < 0.005), and cellular heparan sulfate (p < 0.01), while ADAM17 (p < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 (p < 0.05), hyaluronic acid (p < 0.002), and hyaluronan synthase 1 (p < 0.01). Consequently, the infection by a SARS-CoV-2 spike protein pseudo-typed lentivirus was reduced in cells pretreated with OM-85. All effects of OM-85 were concentration- and time-dependent. The results suggest that OM-85 might reduce the binding of SARS-CoV-2 S-protein to epithelial cells by modification of host cell membrane proteins and specific glycosaminoglycans. Thus, OM-85 might be considered as an add-on for COVID-19 therapy. Full article
(This article belongs to the Special Issue Drug Development for COVID-19)
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15 pages, 3212 KiB  
Article
Anti-SARS-CoV-2 Activity of Extracellular Vesicle Inhibitors: Screening, Validation, and Combination with Remdesivir
by Supasek Kongsomros, Ampa Suksatu, Phongthon Kanjanasirirat, Suwimon Manopwisedjaroen, Somsak Prasongtanakij, Kedchin Jearawuttanakul, Suparerk Borwornpinyo, Suradej Hongeng, Arunee Thitithanyanont and Somchai Chutipongtanate
Biomedicines 2021, 9(9), 1230; https://doi.org/10.3390/biomedicines9091230 - 16 Sep 2021
Cited by 9 | Viewed by 4062
Abstract
The coronavirus disease 2019 (COVID-19) pandemic severely impacts health, economy, and society worldwide. Antiviral drugs against SARS-CoV-2 are urgently needed to cope with this global crisis. It has been found that the biogenesis and release mechanisms of viruses share a common pathway with [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic severely impacts health, economy, and society worldwide. Antiviral drugs against SARS-CoV-2 are urgently needed to cope with this global crisis. It has been found that the biogenesis and release mechanisms of viruses share a common pathway with extracellular vesicles (EVs). We hypothesized that small molecule inhibitors of EV biogenesis/release could exert an anti-SARS-CoV-2 effect. Here, we screened 17 existing EV inhibitors and found that calpeptin, a cysteine proteinase inhibitor, exhibited the most potent anti-SARS-CoV-2 activity with no apparent cytotoxicity. Calpeptin demonstrated the dose-dependent inhibition against SARS-CoV-2 viral nucleoprotein expression in the infected cells with a half-maximal inhibitory concentration (IC50) of 1.44 µM in Vero-E6 and 26.92 µM in Calu-3 cells, respectively. Moreover, calpeptin inhibited the production of infectious virions with the lower IC50 of 0.6 µM in Vero E6 cells and 10.12 µM in Calu-3 cells. Interestingly, a combination of calpeptin and remdesivir, the FDA-approved antiviral drug against SARS-CoV-2 viral replication, significantly enhanced the anti-SARS-CoV-2 effects compared to monotherapy. This study discovered calpeptin as a promising candidate for anti-SARS-CoV-2 drug development. Further preclinical and clinical studies are warranted to elucidate the therapeutic efficacy of calpeptin and remdesivir combination in COVID-19. Full article
(This article belongs to the Special Issue Drug Development for COVID-19)
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28 pages, 4962 KiB  
Article
Computational Study of Potential Galectin-3 Inhibitors in the Treatment of COVID-19
by Maral Aminpour, Marco Cannariato, Angelica Zucco, Elisabetta Di Gregorio, Simone Israel, Annalisa Perioli, Davide Tucci, Francesca Rossi, Sara Pionato, Silvia Marino, Marco A. Deriu, Kiran K. Velpula and Jack A. Tuszynski
Biomedicines 2021, 9(9), 1208; https://doi.org/10.3390/biomedicines9091208 - 13 Sep 2021
Cited by 5 | Viewed by 4112
Abstract
Galectin-3 is a carbohydrate-binding protein and the most studied member of the galectin family. It regulates several functions throughout the body, among which are inflammation and post-injury remodelling. Recent studies have highlighted the similarity between Galectin-3′s carbohydrate recognition domain and the so-called “galectin [...] Read more.
Galectin-3 is a carbohydrate-binding protein and the most studied member of the galectin family. It regulates several functions throughout the body, among which are inflammation and post-injury remodelling. Recent studies have highlighted the similarity between Galectin-3′s carbohydrate recognition domain and the so-called “galectin fold” present on the N-terminal domain of the S1 sub-unit of the SARS-CoV-2 spike protein. Sialic acids binding to the N-terminal domain of the Spike protein are known to be crucial for viral entry into humans, and the role of Galectin-3 as a mediator of lung fibrosis has long been the object of study since its levels have been found to be abnormally high in alveolar macrophages following lung injury. In this context, the discovery of a double inhibitor may both prevent viral entry and reduce post-infection pulmonary fibrosis. In this study, we use a database of 56 compounds, among which 37 have known experimental affinity with Galectin-3. We carry out virtual screening of this database with respect to Galectin-3 and Spike protein. Several ligands are found to exhibit promising binding affinity and interaction with the Spike protein’s N-terminal domain as well as with Galectin-3. This finding strongly suggests that existing Galectin-3 inhibitors possess dual-binding capabilities to disrupt Spike–ACE2 interactions. Herein we identify the most promising inhibitors of Galectin-3 and Spike proteins, of which five emerge as potential dual effective inhibitors. Our preliminary results warrant further in vitro and in vivo testing of these putative inhibitors against SARS-CoV-2 with the hope of being able to halt the spread of the virus in the future. Full article
(This article belongs to the Special Issue Drug Development for COVID-19)
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Review

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20 pages, 6144 KiB  
Review
Current Potential Therapeutic Approaches against SARS-CoV-2: A Review
by Dharmendra Kumar Yadav, Desh Deepak Singh, Ihn Han, Yogesh Kumar and Eun-Ha Choi
Biomedicines 2021, 9(11), 1620; https://doi.org/10.3390/biomedicines9111620 - 4 Nov 2021
Cited by 7 | Viewed by 2650
Abstract
The ongoing SARS-CoV-2 pandemic is a serious threat to public health worldwide and, to date, no effective treatment is available. Thus, we herein review the pharmaceutical approaches to SARS-CoV-2 infection treatment. Numerous candidate medicines that can prevent SARS-CoV-2 infection and replication have been [...] Read more.
The ongoing SARS-CoV-2 pandemic is a serious threat to public health worldwide and, to date, no effective treatment is available. Thus, we herein review the pharmaceutical approaches to SARS-CoV-2 infection treatment. Numerous candidate medicines that can prevent SARS-CoV-2 infection and replication have been proposed. These medicines include inhibitors of serine protease TMPRSS2 and angiotensin converting enzyme 2 (ACE2). The S protein of SARS-CoV-2 binds to the receptor in host cells. ACE2 inhibitors block TMPRSS2 and S protein priming, thus preventing SARS-CoV-2 entry to host cells. Moreover, antiviral medicines (including the nucleotide analogue remdesivir, the HIV protease inhibitors lopinavir and ritonavir, and wide-spectrum antiviral antibiotics arbidol and favipiravir) have been shown to reduce the dissemination of SARS-CoV-2 as well as morbidity and mortality associated with COVID-19. Full article
(This article belongs to the Special Issue Drug Development for COVID-19)
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