SAR based Review on Diverse Heterocyclic Compounds with Various Potential Molecular Targets in the Fight against COVID-19: A Medicinal Chemist Perspective

Abstract

Coronavirus disease (COVID-19) was reported to be transmitted from bats to humans and, became a pandemic in 2020. COVID-19 is responsible for millions of deaths worldwide and still, the numbers are increasing. Further, despite the availability of vaccines, mutation in the virus continuously poses a threat of re-emergence of the more lethal form of the virus. So far, the repurposing of drugs has been exercised heavily for the identification of therapeutic agents against COVID-19, which led FDA to approve many drugs for the same e.g., remdesivir, favipiravir, ribavirin, etc. The anti-COVID drugs explored via other approaches include nirmatrelvir (used in combination with ritonavir as Paxlovid), tixagevimab and cilgavimab (both used in combination with each other) and others. However, these approved drugs failed to achieve a significant clinical outcome. Globally, natural bioactive have also been explored for anti-COVID-19 effects, based on their traditional medicinal values. Although the clinical findings suggest that FDA-approved drugs and natural bioactives can help reducing the overall mortality rate but the significant clinical outcome was not achieved. Therefore, the focus has been shifted towards new drug development. In line with that, a lot of work has been done and still going on to explore heterocyclic compounds as potent anti-COVID-19 drugs. Several heterocyclic scaffolds have been previously reported with potent antiinflammatory, anticancer, anti-viral, antimicrobial and anti-tubercular effects. Few of them are under consideration for clinical trials whereas others are under preclinical investigation. Hence, this review discusses the evidence of rationally designed and tested heterocyclic compounds acting on different targets against COVID-19. The present manuscript will help the researches and will serve as a pivotal resource in the design and development of novel anti-COVID-19 drugs.

Development of 2-chloroquinoline based heterocyclic frameworks as dual inhibitors of SARS-CoV-2 MPro and PLPro

“…Heterocyclic compounds have unique place in medicinal chemistry [ 15 , 16 ] and in the recent years identified as covalent and non-covalent against both M Pro and PL Pro enzymes [ [17] , [18] , [19] , [20] ]. Rational design and testing of heterocyclic compounds acting on different targets against SARS-CoV-2 has been recently reviewed in detail [ 21 ]. Quinoline, a fused heterocyclic compound is a privileged scaffold and a versatile pharmacophore, that is part of antibacterial, anti-tubercular, anticancer, antiviral and local anaesthetic drugs [ [22] , [23] , [24] ].…”