COVID-19 Therapeutic Options Under Investigation

Abstract

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexamethasone have been so far shown to reduce COVID-19-associated death. Here, we provide a review of the potential therapeutic agents being considered for the treatment and management of COVID-19 patients.

Keywords: COVID-19; SARS-CoV-2; adjunctive therapy; antivirals; therapeutics.

Figure 1

The life cycle of SARS-CoV-2 and the mode of action of potential therapeutic molecules. SARS-CoV-2 enters target cells through an endosomal pathway. The S protein of the virus binds to cellular receptor ACE2. Following the entry of the virus into the host cell, the viral RNA is unveiled in the cytoplasm. ORF1a and ORF1ab are translated to produce pp1a and pp1ab polyproteins, which are cleaved by the proteases that are encoded by ORF1a to yield non-structural proteins that form the RNA replicase-transcriptase complex. The polymerase produces a series of subgenomic mRNAs by discontinuous transcription and finally translated into relevant viral proteins. Viral nucleocapsids are assembled from genomic RNA and N protein in the cytoplasm, followed by budding into the lumen of the ERGIC. Virions are then released from the infected cell through exocytosis. ACE2, angiotensin-converting enzyme 2; ER, endoplasmic reticulum; ERGIC, ER-Golgi intermediate compartment. Drugs with potential anti-SARS-CoV-2 activity are depicted on the corresponding stage of the virus life cycle which they are thought to interfere with.