Synthetic small molecule based anti-viral chemical drugs as treatment options for COVID-19: New updates review

Abstract

The SARS-CoV-2 outbreak and subsequent pandemic that began in late 2019 has presented a significant challenge to global health. Currently, numerous small-molecule therapeutic candidates have been developed that can inhibit both the infection and replication of SARS-CoV-2, and may even alleviate cytokine storms and related complications. Additionally, host-targeted drugs that inhibit the cellular transmembrane serine protease (TMPRSS2) can block SARS-CoV-2 from entering cells. When used in combination with chloroquine and dihydroorotate dehydrogenase (DHODH) inhibitors, these therapies can limit the spread of SARS-CoV-2 and reduce the morbidity and mortality of COVID-19 patients. This article provides a comprehensive overview of these small-molecule therapeutics, drawing on insights from medicinal chemistry research. It focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as nucleoside analogues like remdesivir, favipiravir, and ribavirin. The review also examines inhibitors of 3C-like protease (3CLpro), papain-like protease (PLpro), and other potentially innovative active ingredient molecules, discussing their targets, activities, clinical status, and side effects.