Special Issue "Antiviral Drugs 2021"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 31 March 2022.

Special Issue Editor

Prof. Dr. Zoidis Grigoris
E-Mail Website
Guest Editor
Department of Pharmaceutical Chemistry, Panepistimiopolis Zografou-GR, 15771 Athens, Greece
Interests: medicinal chemistry; antiviral agents; trypanocidal agents; anti-HBV drugs; anti-HCV drugs; anti-influenza A agents; anti-Flavivirus agents

Special Issue Information

Dear Colleagues, 

From the beginning of human civilization, viral infections have been part of human life, and still represent one of the greatest burdens for humans and society, with a huge devastating socioeconomic impact. Over the last year, a worst-case scenario of viral pandemic (i.e., severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has threatened millions of lives, while devastating the primal health care systems across the world. Fortunately, the advancement in the field of antiviral drug discovery over the last forty years led to the development of important therapies that intercept human immunodeficiency virus (HIV) replication or cure hepatitis C virus infections in people suffering from liver disease. Nevertheless, according to the World Health Organization (WHO), we are still a long way from achieving suitable treatments for other viral-infection-related diseases such as SARS, HBV, Influenza, and Ebola. Moreover, the emergence of drug resistance that threatens the efficacy of successful therapies used today and the lack of vaccines for many viral pathogens make the discovery and development of antiviral agents an unmet global need. Urged by this global crisis, the field has been involved in an unprecedented endeavor to enhance established antiviral strategies and develop novel and innovative approaches for new classes of antiviral agents targeting different life cycle pathways that are critical for the virus, including viral and host factors and new antiviral modalities.

In the present Special Issue entitled “Antiviral Drugs”, we are inviting the submission of original research articles, letters, and/or reviews from academia, research institutes, not-for-profit organizations, or industry that work on the identification, synthesis, and evaluation of direct-acting antiviral or host-targeting agents that inhibit viral replication or pathogenesis. Furthermore, we also welcome the submission of mechanistic studies of new small organic molecules, metal complexes, and natural products, as well as studies on drug resistance, the in silico design of antiviral agents, and antiviral target validation.

Prof. Dr. Grigoris Zoidis
Guest Editor

Manuscript Submission Information

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Published Papers (6 papers)

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Research

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Communication
Ginkgolic Acid Inhibits Coronavirus Strain 229E Infection of Human Epithelial Lung Cells
Pharmaceuticals 2021, 14(10), 980; https://doi.org/10.3390/ph14100980 (registering DOI) - 26 Sep 2021
Abstract
Since December 2019, the COVID-19 pandemic has affected more than 200 million individuals around the globe and caused millions of deaths. Although there are now multiple vaccines for SARS-CoV-2, their efficacy may be limited by current and future viral mutations. Therefore, effective antiviral [...] Read more.
Since December 2019, the COVID-19 pandemic has affected more than 200 million individuals around the globe and caused millions of deaths. Although there are now multiple vaccines for SARS-CoV-2, their efficacy may be limited by current and future viral mutations. Therefore, effective antiviral compounds are an essential component to win the battle against the family of coronaviruses. Ginkgolic Acid (GA) is a pan-antiviral molecule with proven effective in vitro and in vivo activity. We previously demonstrated that GA inhibits Herpes Simplex Virus 1 (HSV-1) by disrupting viral structure, blocking fusion, and inhibiting viral protein synthesis. Additionally, we reported that GA displays broad-spectrum fusion inhibition encompassing all three classes of fusion proteins, including those of HIV, Ebola, influenza A, and Epstein Barr virus. Here, we report that GA exhibited potent antiviral activity against Human Coronavirus strain 229E (HCoV-229E) infection of human epithelial lung cells (MRC-5). GA significantly reduced progeny virus production, expression of viral proteins, and cytopathic effects (CPE). Furthermore, GA significantly inhibited HCoV-229E even when added post-infection. In light of our findings and the similarities of this family of viruses, GA holds promising potential as an effective antiviral treatment for SARS-CoV-2. Full article
(This article belongs to the Special Issue Antiviral Drugs 2021)
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Article
Discovery of a Novel Tetrapeptide against Influenza A Virus: Rational Design, Synthesis, Bioactivity Evaluation and Computational Studies
Pharmaceuticals 2021, 14(10), 959; https://doi.org/10.3390/ph14100959 - 23 Sep 2021
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Abstract
Influenza is a highly contagious, acute respiratory illness, which represents one of the main health issues worldwide. Even though some antivirals are available, the alarming increase in virus strains resistant to them highlights the need to find new drugs. Previously, Superti et al. [...] Read more.
Influenza is a highly contagious, acute respiratory illness, which represents one of the main health issues worldwide. Even though some antivirals are available, the alarming increase in virus strains resistant to them highlights the need to find new drugs. Previously, Superti et al. deeply investigated the mechanism of the anti-influenza virus effect of bovine lactoferrin (bLf) and the role of its tryptic fragments (the N- and C-lobes) in antiviral activity. Recently, through a truncation library, we identified the tetrapeptides, Ac-SKHS-NH2 (1) and Ac-SLDC-NH2 (2), derived from bLf C-lobe fragment 418–429, which were able to bind hemagglutinin (HA) and inhibit cell infection in a concentration range of femto- to picomolar. Starting from these results, in this work, we initiated a systematic SAR study on the peptides mentioned above, through an alanine scanning approach. We carried out binding affinity measurements by microscale thermophoresis (MST) and surface plasmon resonance (SPR), as well as hemagglutination inhibition (HI) and virus neutralization (NT) assays on synthesized peptides. Computational studies were performed to identify possible ligand–HA interactions. Results obtained led to the identification of an interesting peptide endowed with broad anti-influenza activity and able to inhibit viral infection to a greater extent of reference peptide. Full article
(This article belongs to the Special Issue Antiviral Drugs 2021)
Article
Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds
Pharmaceuticals 2021, 14(9), 892; https://doi.org/10.3390/ph14090892 - 01 Sep 2021
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Abstract
Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main [...] Read more.
Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant in the sub-micromolar range (Ki = 0.81 μM). Two phenylpropene analogs were also tested: the same effect was observed for estragole with a lower potency (Ki = 4.1 μM), whereas anethole was less active. The binding efficiency index of these compounds is remarkably favorable due also to their small molecular mass (MW < 165 Da). We envision that nanomolar inhibition of 3CLpro is widely accessible within the chemical space of simple natural compounds. Full article
(This article belongs to the Special Issue Antiviral Drugs 2021)
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Article
Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1
Pharmaceuticals 2021, 14(8), 715; https://doi.org/10.3390/ph14080715 - 24 Jul 2021
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Abstract
Hg-CATH and Pb-CATH4 are cathelicidins from Heterocephalus glaber and Python bivittatus that have been previously identified as potent antibacterial peptides. However, their antiviral properties were not previously investigated. In this study, their activity against the herpes simplex virus (HSV)-1 was evaluated during primary [...] Read more.
Hg-CATH and Pb-CATH4 are cathelicidins from Heterocephalus glaber and Python bivittatus that have been previously identified as potent antibacterial peptides. However, their antiviral properties were not previously investigated. In this study, their activity against the herpes simplex virus (HSV)-1 was evaluated during primary human keratinocyte infection. Both of them significantly reduced HSV-1 DNA replication and production of infectious viral particles in keratinocytes at noncytotoxic concentrations, with the stronger activity of Pb-CATH4. These peptides did not show direct virucidal activity and did not exhibit significant immunomodulatory properties, except for Pb-CATH4, which exerted a moderate proinflammatory action. All in all, our results suggest that Hg-CATH and Pb-CATH4 could be potent candidates for the development of new therapies against HSV-1. Full article
(This article belongs to the Special Issue Antiviral Drugs 2021)
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Article
Identification of SARS-CoV-2 E Channel Blockers from a Repurposed Drug Library
Pharmaceuticals 2021, 14(7), 604; https://doi.org/10.3390/ph14070604 - 23 Jun 2021
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Abstract
SARS-CoV-2, the etiological agent of the COVID-19 pandemic, is a member of the Coronaviridae family. It is an enveloped virus with ion channels in its membrane, the most characterized of which is the E protein. Therefore, in an attempt to identify blockers of [...] Read more.
SARS-CoV-2, the etiological agent of the COVID-19 pandemic, is a member of the Coronaviridae family. It is an enveloped virus with ion channels in its membrane, the most characterized of which is the E protein. Therefore, in an attempt to identify blockers of the E channel, we screened a library of 2839 approved-for-human-use drugs. Our approach yielded eight compounds that exhibited appreciable activity in three bacteria-based channel assays. Considering the fact that the E channel is the most conserved of all SARS-CoV-2 proteins, any inhibitor of its activity may provide an option to curb the viral spread. In addition, inhibitors can also enhance our ability to understand the exact role played by the E protein during the infectivity cycle. Finally, detailed electrophysiological analyses, alongside in vitro and in vivo studies will be needed to establish the exact potential of each of the blockers identified in our study. Full article
(This article belongs to the Special Issue Antiviral Drugs 2021)
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Review

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Review
Antiviral Therapeutic Approaches for SARS-CoV-2 Infection: A Systematic Review
Pharmaceuticals 2021, 14(8), 736; https://doi.org/10.3390/ph14080736 - 28 Jul 2021
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Abstract
Due to the lack of an etiologic treatment for SARS-CoV-2 and the difficulties involved in developing new drugs, some drugs already approved for other diseases or with efficacy against SARS and MERS, have been used in patients with COVID-19. This systematic review aims [...] Read more.
Due to the lack of an etiologic treatment for SARS-CoV-2 and the difficulties involved in developing new drugs, some drugs already approved for other diseases or with efficacy against SARS and MERS, have been used in patients with COVID-19. This systematic review aims to summarize evidence on the efficacy and safety of five antivirals applied to patients with COVID-19, that have proven to be effective either in vitro studies or in studies on SARS-CoV and MERS.; An intensive search of different databases (Pub Med, WoS, MEDLINE and Cochrane COVID-19 Study Register) has been carried out until the end of April 2021. This systematic review has been conducted according to the PRISMA statement. From each of the included studies, the characteristics of the intervention and comparison groups, demographic data and results were extracted independently; Remdesivir is well tolerated and helps to accelerate clinical improvement but is ineffective in reducing mortality. Favipiravir is safe and shows promising results regarding symptom resolution but does not improve viral clearance. The use of lopinavir/ritonavir has been associated with an increased risk of gastrointestinal adverse events and it has not proven to be effective. No significant differences were observed between patients treated with ribavirin or umifenovir and their respective control groups; Remdesivir and favipiravir are well tolerated and effective in accelerating clinical improvement. This systematic review does not support the use of lopinavir/ritonavir, ribavirin and umifenovir in hospitalized patients with COVID-19. Full article
(This article belongs to the Special Issue Antiviral Drugs 2021)
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