On March 11, 2020, the novel Corona virus disease (COVID-19), was described as a pandemic by World Health Organization (WHO). Globally, the COVID-19 has not only affected the public health socially but also has rigorously affected economically. Substantial declines in income, increase in unemployment, and distractions in the transportation, amenities, and industrial sectors are amongst the major concerns of the pandemic disease extenuation. Furthermore, the governments of most of the countries underestimated the menaces of COVID-19 spread and were typically responsive for the calamities in their respective countries. As outbreak of this pandemic is not likely to wane in the nearby future, preventive actions are prerequisite to prevent infection spread, save people lives and also to save the economic affluence. In this review, based on the present knowledge and available literature, we have demonstrated the various aspects of pre-and post-COVID-19 effects over the social and economic phases worldwide. Moreover, the evidence based data have been summarized regarding threats, social influences, scientific upgrades, moral dynamics, stress and adapting in the pre- and post- COVID-19 situations.
COVID-19, an acute viral pneumonia, has emerged as a devastating pandemic. Drug
repurposing allows researchers to find different indications of FDA-approved or
investigational drugs. In this current study, a sequence of pharmacophore and molecular
modeling-based screening against COVID-19 M
pro
(PDB: 6LU7) suggested a subset of drugs, from
the Drug Bank database, which may have antiviral activity. A total of 44 out of 8823 of
the most promising virtual hits from the Drug Bank were subjected to molecular dynamics
simulation experiments to explore the strength of their interactions with the SARS-CoV-2
M
pro
active site. MD findings point toward three drugs (DB04020, DB12411,
and DB11779) with very low relative free energies for SARS-CoV-2 M
pro
with
interactions at His41 and Met49. MD simulations identified an additional interaction
with Glu166, which enhanced the binding affinity significantly. Therefore, Glu166 could
be an interesting target for structure-based drug design. Quantitative
structural–activity relationship analysis was performed on the 44 most promising
hits from molecular docking-based virtual screening. Partial least square regression
accurately predicted the values of independent drug candidates’ binding energy
with impressively high accuracy. Finally, the EC
50
and CC
50
of 10
drug candidates were measured against SARS-CoV-2 in cell culture. Nilotinib and
bemcentinib had EC
50
values of 2.6 and 1.1 μM, respectively. In
summary, the results of our computer-aided drug design provide a roadmap for rational
drug design of M
pro
inhibitors and the discovery of certified medications as
COVID-19 antiviral therapeutics.
Cytochrome P450 peroxygenases use hydrogen peroxide to hydroxylate long-chain fatty acids by bypassing the use of O 2 and a redox partner. Among the peroxygenases, P450 OleT uniquely performs decarboxylation of fatty acids and production of terminal olefins. This route taken by P450 OleT is intriguing, and its importance is augmented by the practical importance of olefin production. As such, this mechanistic choice merits elucidation. To address this puzzle, we use hybrid QM/ MM calculations and MD simulations for the OleT enzyme as well as for the structurally analogous enzyme, P450 BSβ . The study of P450 OleT reveals that the protonated His85 in the wild-type P450 OleT plays a crucial role in steering decarboxylation activity by stabilizing the corresponding hydroxoiron(IV) intermediate (Cpd II). In contrast, for P450 BSβ in which Q85 replaces H85, the respective Cpd II species is unstable and it reacts readily with the substrate radical by rebound, producing hydroxylation products. As shown, this single-site difference creates in P450 OleT a local electric field (LEF), which is significantly higher than that in P450 BSβ . In turn, these LEF differences are responsible for the different stabilities of the respective Cpd II/radical intermediates and hence for different functions of the two enzymes. P450 BSβ uses the common rebound mechanism and leads to hydroxylation, whereas P450 OleT proceeds via decarboxylation and generates terminal olefins. Olefin production projects the power of a single residue to alter the LEF and the enzyme's function.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.