Abstract

Viral infections pose a persistent threat to human health. The relentless epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health problem, with millions of infections and fatalities so far. Traditional approaches such as random screening and optimization of lead compounds by organic synthesis have become extremely resource- and time-consuming. Various modern innovative methods or integrated paradigms are now being applied to drug discovery for significant resistance in order to simplify the drug process. This review provides an overview of newly emerging antiviral strategies, including proteolysis targeting chimera (PROTAC), ribonuclease targeting chimera (RIBOTAC), targeted covalent inhibitors, topology-matching design and antiviral drug delivery system. This article is dedicated to Prof. Dr. Erik De Clercq, an internationally renowned expert in the antiviral drug research field, on the occasion of his 80th anniversary.

Highlights

  • Emerging infectious diseases have threatened humanity throughout history [1]

  • The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was considered “among the deadliest pandemics of the past century” [8,9], and as of 25 January 2022, confirmed cases of COVID19 reached 352 million with 5.60 million deaths

  • Existing antiviral drugs are facing the dilemma of increasing drug-resistant strains [11], while vaccines often do not work against mutated or novel viruses

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Summary

Introduction

Emerging infectious diseases have threatened humanity throughout history [1]. Infectious diseases have accounted for 20% of global mortality, and viral diseases have caused. The E3 ligase ubiquitylated POI is knocked down by the proteasome [14,15] This methodology mediates the transferapplied of ubiquitin from an enzyme to the POI, and the ubiq has been gradually to the discovery of E2 antiviral agents. TheDGY-08-097 finding confirmed that these degradersHCV were in lessa vulnerable to mutations thatnM), affected ligand bindingthat and the could be employedof to protein inhibit orwas treathelpful viral model The finding confirmed that these small-molecule degraders were les vulnerable to mutations that affected ligand binding and could be employed to inhibit o treat viral variants associated with resistance to traditional inhibitors

Chemical
Ribonuclease
Targeted Covalent Inhibitors
Design
Antiviral Drug Delivery System
The discovery inhibitorypotency potency against a set of HIV-1 subtypes
Findings
Conclusions
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