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The present-day world is severely suffering from the recently emerged SARS-CoV-2. The lack of prescribed drugs for the deadly virus has stressed the likely need to identify novel inhibitors to alleviate and stop the pandemic. In the present high throughput virtual screening study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), and ADME properties to screen natural compounds. It has been documented that many natural compounds display antiviral activities, including anti-SARS-CoV effect. The present study deals with compounds of Natural Product Activity and Species Source (NPASS) database with known biological activity that probably impedes the activity of six essential enzymes of the virus. Promising drug-like compounds were identified, demonstrating better docking score and binding energy for each druggable targets. After an extensive screening analysis, three novel multi-target natural compounds were predicted to subdue the activity of three/ more major drug targets simultaneously. Concerning the utility of natural compounds in the formulation of many therapies, we propose these compounds as excellent lead candidates for the development of therapeutic drugs against SARS-CoV-2.

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According to the Center for Disease Control and Prevention, as of August 23, 94 countries had confirmed 42,954 Monkeypox Virus cases. As specific monkeypox drugs are not yet developed, the treatment depends on repurposed FDA-approved drugs. According to a recent study, the Monkeypox outbreak is caused by a strain with a unique mutation, raising the likelihood that the virus will develop resistance to current drugs by acquiring mutations in the targets of currently used drugs. The probability of multiple mutations in two or more drug targets at a time is always low than mutation in a single drug target. Therefore, we identified 15 triple-targeting FDA-approved drugs that can inhibit three viral targets, including topoisomerase1, p37, and thymidylate kinase, using high throughput virtual screening approach. Further, the molecular dynamics simulation analysis of the top hits such as Naldemedine and Saquinavir with their respective targets reveals the formation of stable conformational changes of the ligand–protein complexes inside the dynamic biological environment. We suggest further research on these triple-targeting molecules to develop an effective therapy for the currently spreading Monkeypox. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-023-10636-4.

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