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Microorganisms
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COVID-19/SARS-CoV-2 Therapeutic Options Development: From Bench to Bedside
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COVID-19/SARS-CoV-2 Therapeutic Options Development: From Bench to Bedside

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 8085

Special Issue Editors

Dr. Samuele Sabbatini

E-Mail Website
Guest Editor
Department of Medicine and Surgery, Medical Microbiology Section, University of Perugia, 06129 Perugia, Italy
Interests: SARS-CoV-2; antivirals; COVID-19; VOCs; Candida albicans; biofilm infections; probiotics; antimicrobial resistance
Special Issues, Collections and Topics in MDPI journals
Dr. Anna Gidari

E-Mail Website
Guest Editor
Department of Medicine and Surgery, Clinic of Infectious Diseases, University of Perugia, 06129 Perugia, Italy
Interests: SARS-CoV-2; COVID-19; antivirals; VOCs; infectious diseases; Staphylococcus aureus; biofilm; antimicrobial resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The global COVID-19 pandemic has had an immense impact on public health, social life, and economies. Less than one year following the discovery of new SARS-CoV-2, many vaccines have been approved and now administered to millions of people around the world; however, unfortunately, SARS-CoV-2 variants of concern (VOCs) have been selected by the continuous transmission between individuals and vaccine pressure. The delay in the administration of these vaccines in developing countries, together with the lack of adhesion of many people to the vaccination campaign, has led to a huge wave of SARS-CoV-2 infections, of which the Omicron variant is the protagonist.

Currently, there are very few available antiviral therapies that have been used against this coronavirus. Many researchers have focused their studies on new or existing antiviral drugs, with the aim of finding effective therapeutic therapies against COVID-19. In addition, various endogenous and natural compounds have been tested and are still under investigation for their role in the pathogenesis of COVID-19.

This Special Issue on the development of COVID-19/SARS-CoV-2 therapeutic options will cover basic aspects of the study of new drugs/compounds or molecules with direct antiviral effects, or those that are implicated in the patient's response to SARS-CoV-2. The discovery of crucial factors in the pathophysiology of COVID-19 could reveal new plausible therapeutic targets against which drugs can be developed and tested.

Dr. Samuele Sabbatini
Dr. Anna Gidari
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. Microorganisms 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 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

  • SARS-CoV-2
  • COVID-19
  • antivirals
  • therapeutic development
  • pathogenesis
  • COVID-19 pathophysiology

Published Papers (3 papers)

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Research

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13 pages, 1262 KiB  
Article
Nelfinavir: An Old Ally in the COVID-19 Fight?
by Anna Gidari, Samuele Sabbatini, Carlo Pallotto, Sabrina Bastianelli, Sara Pierucci, Chiara Busti, Elisabetta Schiaroli and Daniela Francisci
Microorganisms 2022, 10(12), 2471; https://doi.org/10.3390/microorganisms10122471 - 14 Dec 2022
Cited by 1 | Viewed by 1364
Abstract
After almost three years of the pandemic, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is still spreading around the world, causing notable sanitary and social issues. New antiviral therapies are constantly under investigation. However, few options have been approved for the treatment of [...] Read more.
After almost three years of the pandemic, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is still spreading around the world, causing notable sanitary and social issues. New antiviral therapies are constantly under investigation. However, few options have been approved for the treatment of COVID-19. Clinical trials are currently ongoing to evaluate the efficacy of nelfinavir on mild–moderate COVID-19. This study aims to investigate the activity of this compound on SARS-CoV-2 “Variants of Concern” (VOCs), comparing its effectiveness with the approved drugs remdesivir and molnupiravir. The experiments were conducted in a biosafety level 3 facility. In this study, we used a Vero-E6-cell-based infection assay to investigate the in vitro activity of nelfinavir, molnupiravir, and remdesivir. Four strains of SARS-CoV-2 were tested: 20A.EU1, B.1.1.7, P.1, and B.1.617.2. All compounds reached micromolar/submicromolar EC50, EC90, and EC99. Furthermore, the Cmax/EC50 and Cmax/EC90 ratios were >1 for all compounds and all variants tested. Our study demonstrated that nelfinavir, as molnupiravir, and remdesivir are effective in vitro on SARS-CoV-2 variants. Full article
(This article belongs to the Special Issue COVID-19/SARS-CoV-2 Therapeutic Options Development: From Bench to Bedside)
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11 pages, 1704 KiB  
Article
The Combination of Molnupiravir with Nirmatrelvir or GC376 Has a Synergic Role in the Inhibition of SARS-CoV-2 Replication In Vitro
by Anna Gidari, Samuele Sabbatini, Elisabetta Schiaroli, Sabrina Bastianelli, Sara Pierucci, Chiara Busti, Lucia Comez, Valeria Libera, Antonio Macchiarulo, Alessandro Paciaroni, Ilaria Vicenti, Maurizio Zazzi and Daniela Francisci
Microorganisms 2022, 10(7), 1475; https://doi.org/10.3390/microorganisms10071475 - 21 Jul 2022
Cited by 23 | Viewed by 2564
Abstract
Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic; however, the need for orally administered antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify [...] Read more.
Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic; however, the need for orally administered antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using five two-fold serial dilution of compound concentrations ≤EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were performed in triplicate, each being repeated at least three times. The synergistic score was calculated using Synergy Finder version 2. Results: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p < 0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p < 0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p = 0.01) and 13.08 (p < 0.0001), respectively. Conclusion: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro. Full article
(This article belongs to the Special Issue COVID-19/SARS-CoV-2 Therapeutic Options Development: From Bench to Bedside)
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Review

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26 pages, 3465 KiB  
Review
Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A Revaluation of Pauling’s Vitamin C Therapy
by Hideo Yamasaki, Hideyuki Imai, Atsuko Tanaka and Joji M. Otaki
Microorganisms 2023, 11(2), 397; https://doi.org/10.3390/microorganisms11020397 - 03 Feb 2023
Cited by 1 | Viewed by 3366
Abstract
Linus Pauling, who was awarded the Nobel Prize in Chemistry, suggested that a high dose of vitamin C (l-ascorbic acid) might work as a prevention or treatment for the common cold. Vitamin C therapy was tested in clinical trials, but clear [...] Read more.
Linus Pauling, who was awarded the Nobel Prize in Chemistry, suggested that a high dose of vitamin C (l-ascorbic acid) might work as a prevention or treatment for the common cold. Vitamin C therapy was tested in clinical trials, but clear evidence was not found at that time. Although Pauling’s proposal has been strongly criticized for a long time, vitamin C therapy has continued to be tested as a treatment for a variety of diseases, including coronavirus infectious disease 2019 (COVID-19). The pathogen of COVID-19, SARS-CoV-2, belongs to the β-coronavirus lineage, which includes human coronavirus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). This review intends to shed new light on vitamin C antiviral activity that may prevent SARS-CoV-2 infection through the chemical production of nitric oxide (NO). NO is a gaseous free radical that is largely produced by the enzyme NO synthase (NOS) in cells. NO produced by upper epidermal cells contributes to the inactivation of viruses and bacteria contained in air or aerosols. In addition to enzymatic production, NO can be generated by the chemical reduction of inorganic nitrite (NO2−), an alternative mechanism for NO production in living organisms. Dietary vitamin C, largely contained in fruits and vegetables, can reduce the nitrite in saliva to produce NO in the oral cavity when chewing foods. In the stomach, salivary nitrite can also be reduced to NO by vitamin C secreted from the epidermal cells of the stomach. The strong acidic pH of gastric juice facilitates the chemical reduction of salivary nitrite to produce NO. Vitamin C contributes in multiple ways to the host innate immune system as a first-line defense mechanism against pathogens. Highlighting chemical NO production by vitamin C, we suggest that controversies on the therapeutic effects of vitamin C in previous clinical trials may partly be due to less appreciation of the pleiotropic functions of vitamin C as a universal bioreductant. Full article
(This article belongs to the Special Issue COVID-19/SARS-CoV-2 Therapeutic Options Development: From Bench to Bedside)
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