Small-molecule metabolites in SARS-CoV-2 treatment: a comprehensive review

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread all over the world. In this respect, traditional medicinal chemistry, repurposing, and computational approaches have been exploited to develop novel medicines for treating this condition. The effectiveness of chemicals and testing methods in the identification of new promising therapies, and the extent of preparedness for future pandemics, have been further highly advantaged by recent breakthroughs in introducing noble small compounds for clinical testing purposes. Currently, numerous studies are developing small-molecule (SM) therapeutic products for inhibiting SARS-CoV-2 infection and replication, as well as managing the disease-related outcomes. Transmembrane serine protease (TMPRSS2)-inhibiting medicinal products can thus prevent the entry of the SARS-CoV-2 into the cells, and constrain its spreading along with the morbidity and mortality due to the coronavirus disease 2019 (COVID-19), particularly when co-administered with inhibitors such as chloroquine (CQ) and dihydroorotate dehydrogenase (DHODH). The present review demonstrates that the clinical-stage therapeutic agents, targeting additional viral proteins, might improve the effectiveness of COVID-19 treatment if applied as an adjuvant therapy side-by-side with RNA-dependent RNA polymerase (RdRp) inhibitors.