Title:Indirect-Acting Pan-Antivirals vs. Respiratory Viruses: A Fresh Perspective on Computational Multi-Target Drug Discovery
Volume: 21
Issue: 30
Author(s): Valeria V. Kleandrova, Marcus T. Scotti and Alejandro Speck-Planche*
Affiliation:
- Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900, João Pessoa,Brazil
Keywords:
Antiviral, Caspase-1, Coronaviruses, Indirect-acting pan-antiviral, Influenza, Multi-target, PTML, STING, TLR7,
TNF-α.
Abstract: Respiratory viruses continue to afflict mankind. Among them, pathogens such as coronaviruses
[including the current pandemic agent known as severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2)] and the one causing influenza A (IAV) are highly contagious and deadly.
These can evade the immune system defenses while causing a hyperinflammatory response that
can damage different tissues/organs. Simultaneously targeting several immunomodulatory proteins
is a plausible antiviral strategy since it could lead to the discovery of indirect-acting pan-antiviral (IAPA)
agents for the treatment of diseases caused by respiratory viruses. In this context, computational
approaches, which are an essential part of the modern drug discovery campaigns, could accelerate
the identification of multi-target immunomodulators. This perspective discusses the usefulness
of computational multi-target drug discovery for the virtual screening (drug repurposing) of IAPA
agents capable of boosting the immune system through the activation of the toll-like receptor 7 (TLR7)
and/or the stimulator of interferon genes (STING) while inhibiting key inflammation-related
proteins such as caspase-1 and tumor necrosis factor-alpha (TNF-α).