Nature-Derived Hit, Lead, and Drug-Like Small Molecules: Current Status and Future Aspects Against Key Target Proteins of Coronaviruses.

Md Junaid, Yeasmin Akter, Aysha Siddika, S M Abdul Nayeem, Afsana Nahrin, Syeda Samira Afrose, Md Muzahid Ahmed Ezaj, Muhammad Shaiful Alam

Journal: Mini reviews in medicinal chemistry 2022;22(3):498-549

PMID: 34353257

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Abstract

BACKGROUND

COVID-19 pandemic, the most unprecedented event of the year 2020, has brought millions of scientists worldwide in a single platform to fight against it. Though several drugs are now in the clinical trial, few vaccines are available on the market already, but the lack of an effect of those is making the situation worse.

AIM OF THE STUDY

In this review, we demonstrated comprehensive data of natural antiviral products showing activities against different proteins of Human Coronaviruses (HCoV) that are responsible for its pathogenesis. Furthermore, we categorized the compounds into the hit, lead, and drug based on the IC50/EC50 value, drug-likeness, and lead-likeness test to portray their potentiality to be a drug. We also demonstrated the present status of our screened antiviral compounds with respect to clinical trials and reported the lead compounds that can be promoted to clinical trial against COVID-19.

METHODS

A systematic search strategy was employed focusing on Natural Products (NPs) with proven activity (in vitro, in vivo, or in silico) against human coronaviruses, in general, and data were gathered from databases like PubMed, Web of Science, Google Scholar, SciVerse, and Scopus. Information regarding clinical trials retrieved from the Clinical Trial Database.

RESULTS

Total "245" natural compounds were identified initially from the literature study. Among them, Glycyrrhizin, Caffeic acid, Curcumin is in phase 3, and Tetrandrine, Cyclosporine, Tacrolimus, Everolimus are in phase 4 clinical trial. Except for Glycyrrhizin, all compounds showed activity against COVID-19.

CONCLUSION

In summary, our demonstrated specific small molecules with lead and drug-like capabilities clarified their position in the drug discovery pipeline and proposed future research against COVID-19.

Address: Natural Products Research Division, Advanced Bioinformatics, Computational Biology and Data Science Laboratory, Chattogram, Bangladesh.; Department of Biotechnology & Genetic Engineering, Noakhali Science & Technology University, Chattogram, Bangladesh.; Department of Chemistry, University of Chittagong, Chittagong, Bangladesh.; Department of Pharmacy, University of Science and Technology Chittagong, Bangladesh.; Department of Genetic Engineering and Biotechnology, University of Chittagong, Chittagong, Bangladesh.

DOI: 10.2174/1389557521666210805113231

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MeSH Terms: Antiviral Agents, Biological Products, Clinical Trials, Phase III as Topic, Clinical Trials, Phase IV as Topic, Humans, Pandemics, SARS-CoV-2, COVID-19 Drug Treatment