ABSTRACT
The endeavor has been attempted to present a review on the evolution of modern age drug discovery in India. The contribution of next generation therapeutics options microbial metabolites and the computational drug discovery aspects to the global market from India have been represented. Microbial metabolites such as lipopeptides and peptide therapeutics are gaining worldwide importance due to their multiple applications as broad-spectrum antimicrobial, antiviral, anticancer properties etc. Due to the surge of microbial resistance, tumor resistance, and ongoing pandemic due to constantly mutating corona virus, there is a need to develop next-generation therapeutics options from natural origin, less toxic to the environment, and have higher specificity towards target. Small molecule therapeutics are certainly less specific towards cancer targets hence the cytotoxicity is a major issue in cancer treatment while drug resistance due to the mutations are coming as challenges every day for drug discovery researchers. Microbial lipopeptide reserves a sweet spot in between the small molecule inhibitors and peptide therapeutics because of their amphiphilic compounds consist of a fatty acid side chain and a cyclic peptide moiety of hydrophilic nature. The computational drug discovery approach accelerates the drug discovery process due to the advancement in supercomputer facilities provided by various funding agencies such as the Department of Biotechnology (DBT) and the Department of Science and Technology (DST) in India. The current review article is focusing light on the research contribution of Indian Scientists and Govt. of India in the field of lipopeptide-based research and applications of Computer-aided drug discovery.
ABSTRACT
The coronavirus disease 2019 (COVID-19) rapidly spread across the globe, infecting millions and causing hundreds of deaths. It has been now around three years but still, it remained a serious threat worldwide, even after the availability of some vaccines. Bio-surfactants are known to have antiviral activities and might be a potential alternative for the treatment of SARS-CoV-2 infection. In the present study, we have isolated and purified, a surfactin-like lipopeptide produced by a probiotic bacterial strain Bacillus clausii TS. Upon purification and characterization with MALDI analysis, the molecular weight of the lipopeptide is confirmed as 1037 Da (similar to surfactin C) which is known to have antiviral activities against various enveloped viruses. Purified surfactin-like lipopeptide showed efficient binding and inhibition of SARS-CoV-2 spike (S1) protein, revealed by competitive ELISA assay. Further, we have explored the complete thermodynamics of the inhibitory binding of surfactin-like lipopeptide with S1 protein using isothermal titration calorimetric (ITC) assay. ITC results are in agreement with ELISA with a binding constant of 1.78 × 10-4 M-1. For further validation of the inhibitory binding of surfactin-like lipopeptide with S1 protein and its receptor binding domain (RBD), we performed molecular docking, dynamics, and simulation experiments. Our results suggested that surfactin could be a promising drug agent for the spike protein targeting drug development strategy against SARS-CoV-2 and other emerging variants.Communicated by Ramaswamy H. Sarma.
ABSTRACT
The world is facing one of its largest Pandemics ever, “The COVID-19”! The giant leaps taken in medicine and research have bowed down before a teeny tiny virus. This has conveyed to mankind that the armamentariums we possess against viruses are futile. Most of the drugs provide symptomatic relief only with few unswervingly being able to destroy the virus. Nonetheless, the scientific community is on the overtime for new boulevards of research and ways to defeat this threat. Biosurfactants (BSs) were stumbled upon as a plausible gold mine! In fact, its antimicrobial and antiadhesive properties have been well accepted. It is now postulated to be of aid in preventing the spread of viruses, that is, as a disinfecting agent, as an antiviral by curing symptoms occurring in the incubation period, killing directly the virus-infected cells and also as a drug delivery system. This chapter aims to provide an insight into what BSs are and their enormous potentials in dealing with Respiratory viruses especially the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). © 2022 Elsevier Inc. All rights reserved.
ABSTRACT
The COVID-19 pandemic had anomalous yet inevitable impacts on the world's economies, healthcare systems, and all other aspects of life. Researchers began to uncover hidden routes to find a new horizon of hope using underrated resources. Biosurfactants are sustainable biomolecules with an active surface, unique characteristics, and extensive uses. Bacillus species showed the highest amount of biosurfactant activities and Bacillus subtilis is one of them. The antiviral, antimicrobial, and anti-inflammatory activity of B. subtilis was proven recently. The great advantage is its non-toxic nature. Pro-inflammatory cytokines including IL-1 ß, 6, 8, 12, 18, and TNF-(α are secreted in higher amounts when neutrophils and monocytes are triggered by biosurfactant bacteria. This point of view furnishes the potential application of B. subtilis and its biomolecules against COVID-19, either in the form of a vaccine/therapeutic agent, for a greener environment, healthier life, and environmental sustainability. Further in vivo and clinical trials are needed to validate this hypothesis.