Approaches and advances in the development of potential therapeutic targets and antiviral agents for the management of SARS-CoV-2 infection

Abstract

Virus onslaughts continue to spread fear and cause rampage across the world every now and then. The twenty first century is yet again witnessing a gross global pandemic, Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Globally no vaccines or drug specific to COVID-19 is available. Corona viruses have been in mutual relationship with humans and other hosts over many decades though aggressive zoonotic strains have caused havoc. Zoonotic emergent corona viruses prior to SARS-COV-2 included severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the former leading to aggressive infectious spread and the later with high mortality rate. Although they emerged in the early period of the twenty first century, resilient biomedical and expertise in pharmaceutical domain could not appropriate any proprietary therapeutics. Studies envisaged towards curtailing their spread employed different stages of the virus life cycle with all zoonotic coronaviruses (CoVs) sharing genomic and structural similarities. Hence the strategies against SARS-CoV and MERS-CoV could prove effective against the recent outbreak of SAR-CoV-2. The review unravels key events involved in the lifecycle of SARS-CoV-2 while highlighting the possible avenues of therapy. The review also holds the scope in better understanding a broad-spectrum antivirals, monoclonal antibodies and small molecule inhibitors against viral glycoproteins, host cell receptor, viral mRNA synthesis, RNA-dependent RNA polymerase (RdRp) and viral proteases in order to design and develop antiviral drugs for SARS-CoV-2.

Broad-Spectrum Anti-coronavirus Vaccines and Therapeutics to Combat the Current COVID-19 Pandemic and Future Coronavirus Disease Outbreaks

“…Because of the presence of high-titer nAbs in convalescent patients, convalescent plasma therapy has been applied in clinics to treat several contagious diseases, including SARS, MERS, and COVID-19. However, it is limited by the availability of patient plasma, thus calling for research and development of nAbs against SARS-CoV-2 and SARS-CoV (Krishna et al, 2020).…”

SARS-CoV-2: Pathogenesis, Molecular Targets and Experimental Models

“…Targeting the molecular pathways involved in the pathogenesis might provide a new avenue toward managing SARS-CoV-2 infection (Liu et al, 2021). Several molecular targets were explored to design and develop specific antiviral drugs for SARS-CoV-2 infection (Krishna et al, 2020). Computational and molecular docking studies explore spike S1 protein as a potential molecular target for developing effective therapeutic inhibitors .…”

“…The SARS-CoV-2 binds through the RBD of the S protein and ACE-2 receptor of the host cells (Figure 4). Attempts have also been made to develop novel therapeutic recombinant ACE-2 antibodies, ACE inhibitors, AT1R blockers (Krishna et al, 2020). The role of recombinant human ACE-2 in ARDS therapy has already been proved (Zhang and Baker, 2017).…”

Biology and Pathogenesis of SARS-CoV-2: Understandings for Therapeutic Developments against COVID-19

“…The first ORFa/b (replicase (Rep) gene) encodes 15 or 16 non-structural proteins (nsps) (1–15 or 1–16 nsps). The nsps are required for replication of the virus [ 12 , 17 , 18 ]. ORF1a/b from the 5′-capped RNA genomes is translated to produce a shorter polyprotein (pp1a, including nsps 1–11) or a longer polyprotein (pp1ab, including nsp1–10 and nsp12–16) based on whether the stop codon is recognized or bypassed at the end of ORF1a, respectively.…”