COVID-19: Vaccine Delivery System, Drug Repurposing and Application of Molecular Modeling Approach

Abstract

The acute respiratory syndrome coronavirus (SARS-CoV-2) has spread across the world, resulting in a pandemic COVID-19 which is a human zoonotic disease that is caused by a novel coronavirus (CoV) strain thought to have originated in wild or captive bats in the initial COVID outbreak region. The global COVID-19 outbreak started in Guangdong Province, China’s southernmost province. The global response to the COVID-19 pandemic has been hampered by the sheer number of infected people, many of whom need intensive care before succumbing to the disease. The epidemic is being handled by a combination of disease control by public health interventions and compassionate treatment for those who have been impacted. There is no clear anti-COVID-19 medication available at this time. However, the need to find medications that can turn the tide has led to the development of a number of investigational drugs as potential candidates for improving outcomes, especially in the severely and critically ill. Although many of these adjunctive medications are still being studied in clinical trials, professional organizations have attempted to define the circumstances in which their use is deemed off-label or compassionate. It is important to remind readers that new information about COVID-19’s clinical features, treatment options, and outcomes is released on a regular basis. The mainstay of treatment remains optimized supportive care, and the therapeutic effectiveness of the subsequent agents is still being studied.

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and MPROof SARS-CoV-2

“…The immediate implication of these findings is uncertain beyond the desirable recommendation that lower doses of folic acid should be the target of future possible utilization of Folic acid in SARS-CoV-2 infections. This is contrary to the suggestion of Asad et al 22 that higher dose of folic acid would be beneficial in COVID-19; though the suggestion was based on studies that examined the inhibition of Spike protein by folic acid 23 . Folic acid also significantly inhibits SARS-CoV-2 Papain like protease and at concentrations and IC 50 that are also achievable at routine therapeutic doses.…”

Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2

“…The immediate implication of these findings is uncertain beyond the desirable recommendation that lower doses of folic acid should be the target of future possible utilization of folic acid in SARS-CoV-2 infections. This is contrary to the suggestion of Asad and Shuja (2021) that a higher dose of folic acid would be beneficial in COVID-19, though the suggestion was based on studies that examined the inhibition of Spike protein by folic acid (Abd El Hadi et al, 2021). Folic acid also significantly inhibits SARS-CoV-2 papain-like protease at concentrations and IC 50 that is also achievable at routine therapeutic doses.…”

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

“…For replication, the virus uses its own proteinases such as papain-like protease (PLpro) and chemotrypsin-like protease (3CLpro), forming a replicase–transcriptase complex (RTC). The major enzyme of RTC is an RNA-dependent RNA polymerase (RdRp), which catalyzes the replication of positive mRNA to form the genome of the viral particle [ 21 , 22 ]. The positive mRNA (+, sense), in contrast to the negative mRNA (–, antisense), does not require transcription and is immediately used for the synthesis of viral proteins.…”

“…It has been established that the extent of the ACE2 receptor binding to the SARS-CoV-2 virus underlies the pathogenesis of infection and the development of unfavorable outcomes of COVID-19 [ 21 ]. ACE is the key activator of the renin–angiotensin–aldosterone system [ 58 ].…”