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[Display omitted] • The present review showcases the major pharmaceutical drug targets that can be used to fight against the SARS-CoV-2 pandemic. • Nonstructural protein inhibitors are essential in preventing host cell entry of coronaviruses and are thoroughly discussed. • Potential SARS-CoV-2 drug targets, including their structures, effects and potential impacts, are reviewed. • Small-molecule therapeutics and their modes of disease suppression are explained in detail. The SARS-CoV-2 outbreak and pandemic that began near the end of 2019 has posed a challenge to global health. At present, many candidate small-molecule therapeutics have been developed that can inhibit both the infection and replication of SARS-CoV-2 and even potentially relieve cytokine storms and other related complications. Meanwhile, host-targeted drugs that inhibit cellular transmembrane serine protease (TMPRSS2) can prevent SARS-CoV-2 from entering cells, and its combination with chloroquine and dihydroorotate dehydrogenase (DHODH) inhibitors can limit the spread of SARS-CoV-2 and reduce the morbidity and mortality of patients with COVID-19. The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin. This review also covers inhibitors of 3C-like protease (3CLpro), papain-like protease (PLpro) and other potentially innovative active ingredient molecules, describing their potential targets, activities, clinical status and side effects. [ABSTRACT FROM AUTHOR]

The widespread nature of several viruses is greatly credited to their rapidly altering RNA genomes that enable the infection to persist despite challenges presented by host cells. Within the RNA genome of infections is RNA-dependent RNA polymerase (RdRp), which is an essential enzyme that helps in RNA synthesis by catalysing the RNA template-dependent development of phosphodiester bonds. Therefore, RdRp is an important therapeutic target in RNA virus-caused diseases, including SARS-CoV-2. In this review, we describe the promising RdRp inhibitors that have been launched or are currently in clinical studies for the treatment of RNA virus infections. Structurally, nucleoside inhibitors (NIs) bind to the RdRp protein at the enzyme active site, and nonnucleoside inhibitors (NNIs) bind to the RdRp protein at allosteric sites. By reviewing these inhibitors, more precise guidelines for the development of more promising anti-RNA virus drugs should be set, and due to the current health emergency, they will eventually be used for COVID-19 treatment. Image 1 • This article provides an overview of RdRp inhibitors that have been launched or are in clinical studies for the treatment of RNA virus infections, including COVID-19. • Nucleoside inhibitors (NIs) exhibit broad-spectrum antiviral activity but pose a more serious toxicity risk than non-nucleoside inhibitors (NNIs) because high dosages of NIs result in accumulation in plasma. • Structurally diverse NNIs are endowed with high potential activities but tend to induce drug resistance due to the RdRp allosteric site. [ABSTRACT FROM AUTHOR]