New Perspective of Antiviral Drugs

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

Deadline for manuscript submissions: 31 August 2026 | Viewed by 1434

Special Issue Editor


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Guest Editor
Department of Pharmacy, Division of Pharmaceutical Chemistry, Panepistimiopolis Zografou-GR, 15771 Athens, Greece
Interests: medicinal chemistry; antiviral agents; anticancer agents; trypanocidal agents; anti-HBV drugs; anti-HCV drugs; anti-influenza A agents; anti-flavivirus agents
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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 a viral pandemic (i.e., severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has threatened millions of lives, while devastating the primary 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 “New Perspective of 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.

Dr. Grigoris Zoidis
Guest Editor

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Keywords

  • antiviral drugs
  • antiviral agents
  • small organic molecules
  • metal complexes
  • natural products

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Published Papers (1 paper)

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Research

41 pages, 6784 KB  
Article
Marine Streptomyces-Derived Lipids Inhibit SARS-CoV-2 3CLpro Through In Vitro and Predicted Multi-Site Binding Mechanisms
by Doralyn S. Dalisay, Jomari C. Mateo, Jade Joshua R. Teodosio, Leighiara S. de Guzman, Neaven Bon Joy M. Marcial, Dion Paul C. Caspe, Lex Aliko P. Balida and Jamia Azdina Jamal
Pharmaceuticals 2026, 19(2), 294; https://doi.org/10.3390/ph19020294 - 10 Feb 2026
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Abstract
Background: The SARS-CoV-2 3CLpro is essential for viral replication and an attractive target for antiviral intervention. While most strategies target the catalytic site, recent studies suggest that the dimerization interface and cryptic allosteric pockets offer alternative mechanisms for inhibition. Objective: This [...] Read more.
Background: The SARS-CoV-2 3CLpro is essential for viral replication and an attractive target for antiviral intervention. While most strategies target the catalytic site, recent studies suggest that the dimerization interface and cryptic allosteric pockets offer alternative mechanisms for inhibition. Objective: This study investigated lipid metabolites from the marine sediment-derived Streptomyces sp. DSD454T as potential multi-site 3CLpro inhibitors. Methods: Metabolites were extracted from cultured biomass and characterized using LCMS-QTOF, MS/MS (LCMS-TQ), and 1H NMR, with identities confirmed against authentic standards. 3CLpro inhibition was assessed using a FRET-based assay, and ligand–protein interactions were evaluated through molecular docking and MM/GBSA calculations. Lipid content and comparative lipidomic signatures were examined across bioactive Streptomyces strains through LCMS-TQ and BODIPYTM 493/503 staining. Results: Palmitoleic and linoleic acids were identified as major constituents and inhibited SARS-CoV-2 3CLpro with IC50 values of 1.59 µg/mL (6.25 µM) and 5.29 µg/mL (18.88 µM). Molecular docking predicted that both fatty acids bind not only to the catalytic site but also to the dimerization interface and cryptic allosteric pocket. Additional lipids, including 9-heptadecenoic acid, linolenic acid, 9-HODE, and monoacylglycerols such as aggrecerides A–C and glyceryl-based lipids, showed similarly favorable multi-site binding profiles. Streptomyces sp. DSD454T also exhibited substantial lipid accumulation (~63% of crude extract). Across bioactive Streptomyces strains, a conserved lipid signature correlated strongly with 3CLpro inhibition. Conclusions: This study highlights the potential of microbial lipids as promising scaffolds for developing catalytic and allosteric SARS-CoV-2 3CLpro inhibitors and underscore marine Streptomyces as a valuable source of structurally simple yet mechanistically versatile antiviral metabolites. Full article
(This article belongs to the Special Issue New Perspective of Antiviral Drugs)
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