Chemical system biology approach to identify multi-targeting FDA inhibitors for treating COVID-19 and associated health complications

Abstract

In view of many European countries and the USA leading to the second wave of COVID-19 pandemic, winter season, the evolution of new mutations in the spike protein, and no registered drugs and vaccines for COVID-19 treatment, the discovery of effective and novel therapeutic agents is urgently required. The degrees and frequencies of COVID-19 clinical complications are related to uncontrolled immune responses, secondary bacterial infections, diabetes, cardiovascular disease, hypertension, and chronic pulmonary diseases. It is essential to recognize that the drug repurposing strategy so far remains the only means to manage the disease burden of COVID-19. Despite some success of using single-target drugs in treating the disease, it is beyond suspicion that the virus will acquire drug resistance by acquiring mutations in the drug target. The possible synergistic inhibition of drug efficacy due to drug-drug interaction cannot be avoided while treating COVID-19 and allied clinical complications. Hence, to avoid the unintended development drug resistance and loss of efficacy due to drug-drug interaction, multi-target drugs can be promising tools for the most challenging disease. In the present work, we have carried out molecular docking studies of compounds from the FDA approved drug library, and the FDA approved and passed phase −1 drug libraries with ten therapeutic targets of COVID-19. Results showed that known drugs, including nine anti-inflammatory compounds, four antibiotics, six antidiabetic compounds, and one cardioprotective compound, could effectively inhibit multiple therapeutic targets of COVID-19. Further in-vitro , in vivo , and clinical studies will guide these drugs' proper allocation to treat COVID-19. Communicated by Ramaswamy H. Sarma

Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies

“…The remaining three articles 31 , 32 , 33 , 34 were eliminated Table S1 . At the end of this screening stage, three review articles 32 , 35 , 36 , nine computational studies 31 , 34 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , three none-helicase studies 44 , 45 , 46 , three non-coronavirus studies 47 , 48 , 49 and four unrelated studies 25 , 50 , 51 , 52 were excluded from the analysis. One study was excluded after full review since it was a computation-based.…”

Nanobody-peptide-conjugate (NPC) for passive immunotherapy against SARS-CoV-2 variants of concern (VoC): a prospective pan-coronavirus therapeutics

“…The focus is on a subset of mutants that can undergo mutations, exacerbate the disease status, and elude the established treatment procedure, ensuing in a spike in death toll figures. Looking at the global risk quotient, WHO has addressed these mutants as variants of concern; by now, Alpha, Beta, Gamma, Delta, Omicron, and their sub-lineages have been acknowledged as the established VoCs originating as outbreak epicenters across several continents [ 2 , 62 , 63 ].…”

Identification of FDA-approved drugs with triple targeting mode of action for the treatment of monkeypox: a high throughput virtual screening study

“…As the standard drug discovery approach takes years, the Drug repurposing approach has been widely adopted to tackle the rising trend of Monkeypox and its severe repercussions [ 45 ]. The distinct benefits of repurposed medications in treating human diseases have been thoroughly described [ 22 ]. For instance, thalidomide, a drug used against angina, has been repurposed to cure leprosy, and many more drugs have been reported in the Drug repurposing process [ 46 ].…”

“…A docking score/energy defined the binding potential of each ligand molecule. The compounds with a lower docking score represent the higher binding affinity and vice-versa[ 22 ]. The binding poses of the protein-ligand docked complexes were analyzed with the help of PyMol software [ 23 ].…”