Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (RMSF) that can also be calculated from molecular dynamics simulations. We provide a mathematical derivation showing that, given a set of conservative assumptions, a root mean-square ensemble-average of an all-against-all distribution of pairwise RMSD for a single molecular species, (1/2), is directly related to average B-factors () and (1/2). We show this relationship and explore its limits of validity on a heterogeneous ensemble of structures taken from molecular dynamics simulations of villin headpiece generated using distributed-computing techniques and the Folding@Home cluster. Our results provide a basis for quantifying global structural diversity of macromolecules in crystals directly from x-ray experiments, and we show this on a large set of structures taken from the Protein Data Bank. In particular, we show that the ensemble-average pairwise backbone RMSD for a microscopic ensemble underlying a typical protein x-ray structure is approximately 1.1 A, under the assumption that the principal contribution to experimental B-factors is conformational variability.

Determination of ensemble-average pairwise root mean-square deviation from experimental B-factors.

COVID-19 is a viral disease caused by a new severe acute respiratory syndrome (SARS-CoV-2), which has quickly resulted in a pandemic. As a great threat to global public health, the development of a treatment has become vital, and a rush to find a cure has mobilized researchers from all areas across the world. Synthetic drugs, such as hydroxychloroquine, have gained attention. However, the efficacy of repositioned drugs is still under evaluation, and besides, some severe side effects are a cause for concern. This emphasizes the urgency for treatment options, which can be both safe and effective. With this in mind, natural products could be an important resource in the development of COVID-19 treatment, as they have already contributed in the past to treatments against other viruses, such as HIV, MERS-CoV, and influenza. Natural products are described long term as bioactive substances and some phytochemical classes such as flavonoids, alkaloids, and peptides are known antiviral bioproducts, and have been virtually tested with success against COVID-19. However, important issues still need to be addressed as to their bioavailability and true efficacy in vivo. This review intends to systematically evaluate the natural metabolites that could potentially be used against this new disease looking at their natural sources, mechanism of action and previous pharmacological usages. The aim is to provide a starting point for this research area in order to speed up the establishment of anti-SARS-CoV-2 bioproducts.

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Natural products' role against COVID-19

COVID-19, a disease induced by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), has been the cause of a worldwide pandemic. Though extensive research works have been reported in recent days on the development of effective therapeutics against this global health crisis, there is still no approved therapy against SARS-CoV-2. In the present study, plant-synthesized secondary metabolites (PSMs) have been prioritized to make a review focusing on the efficacy of plant-originated therapeutics for the treatment of COVID-19. Plant metabolites are a source of countless medicinal compounds, while the diversity of multidimensional chemical structures has made them superior to treat serious diseases. Some have already been reported as promising alternative medicines and lead compounds for drug repurposing and discovery. The versatility of secondary metabolites may provide novel antibiotics to tackle MDR (Multi-Drug Resistant) microbes too. This review attempted to find out plant metabolites that have the therapeutic potential to treat a wide range of viral pathogens. The study includes the search of remedies belonging to plant families, susceptible viral candidates, antiviral assays, and the mode of therapeutic action; this attempt resulted in the collection of an enormous number of natural therapeutics that might be suggested for the treatment of COVID-19. About 219 plants from 83 families were found to have antiviral activity. Among them, 149 plants from 71 families were screened for the identification of the major plant secondary metabolites (PSMs) that might be effective for this pandemic. Our investigation revealed that the proposed plant metabolites can serve as potential anti- SARS-CoV-2 lead molecules for further optimization and drug development processes to combat COVID-19 and future pandemics caused by viruses. This review will stimulate further analysis by the scientific community and boost antiviral plant-based research followed by novel drug designing.

Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic

The study aims to evaluate the potency of two hundred natural antiviral phytocompounds against the active site of the Severe Acquired Respiratory Syndrome - Coronavirus − 2 (SARS-CoV-2) Main-Protea...

Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease.

The novel coronavirus SARS-CoV-2 disease "COVID-19" emerged in China and rapidly spread to other countries; due to its rapid worldwide spread, the WHO has declared this as a global emergency. As there is no specific treatment prescribed to treat COVID-19, the seeking of suitable therapeutics among existing drugs seems valuable. The structure availability of coronavirus macromolecules has encouraged the finding of conceivable anti-SARS-CoV-2 therapeutics through in silico analysis. The results reveal that quinoline,1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI) and saquinavir strongly interact with the active site (Cys-His catalytic dyad), thereby are predicted to hinder the activity of SARS-CoV-2 3CLpro. Out of 113 quinoline-drugs, elvitegravir and oxolinic acid are able to interact with the NTP entry-channel and thus interfere with the RNA-directed 5'-3' polymerase activity of SARS-CoV-2 RdRp. The bioactivity-prediction results also validate the outcome of the docking study. Moreover, as SARS-CoV-2 Spike-glycoprotein uses human ACE2-receptor for viral entry, targeting the Spike-RBD-ACE2 has been viewed as a promising strategy to control the infection. The result shows rilapladib is the only quinoline that can interrupt the Spike-RBD-ACE2 complex. In conclusion, owing to their ability to target functional macromolecules of SARS-CoV-2, along with positive ADMET properties, quinoline,1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI), saquinavir, elvitegravir, oxolinic acid, and rilapladib are suggested for the treatment of COVID-19.

Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis

OBJECTIVE: Currently, Coronavirus COVID-19 is spreading worldwide very rapidly and its control is very difficult because there is no effective vaccine or drugs available in markets. This virus can infect both animals and people and cause illnesses of the respiratory tract. WHO has declared Coronavirus as pandemic and the whole world is fighting against Coronavirus. Globally, more than 199,478 people have been diagnosed with COVID-19. As of March 18, 2020, more than 167 countries have been affected and more than 8000 deaths have been reported. The main country being affected is China followed by Italy, Iran, Spain, France, and the USA. MATERIALS AND METHODS: Since there are no effective drugs available against Coronavirus, we conducted virtual screening of phytochemicals to find novel compounds against this virus. Hence, we created a phytochemical library of 318 phytochemicals from 11 plants which have been reported as antiviral, antibacterial and antifungal activity. The phytochemical library was subjected to virtual screening against molecular targets; Main protease (Mpro) and Angiotensin-Converting Enzyme 2 (ACE2). RESULTS: Top 10 compounds were selected from each target which had better and significantly low binding energy as compared to the reference molecule. CONCLUSIONS: Based on the binding energy score, we suggest that these compounds can be tested against Coronavirus and used to develop effective antiviral drugs.

In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking.

Xanthomonas oryzae pv. Oryzae (Xoo) causes bacterial leaf blight (BLB) of rice which results in a huge loss in production. Many chemicals are used to control BLB disease. However, these chemicals a...

Molecular docking and molecular dynamics simulation approach to screen natural compounds for inhibition of Xanthomonas oryzae pv. Oryzae by targeting peptide deformylase.

The outbreak of SARS-CoV-2 and deaths caused by it all over the world have imposed great concern on the scientific community to develop potential drugs to combat Coronavirus disease-19 (COVID-19) In this regard, lichen metabolites may offer a vast reservoir for the discovery of antiviral drug candidates Therefore, to find novel compounds against COVID-19, we created a library of 412 lichen compounds and subjected to virtual screening against the SARS-CoV-2 Main protease (Mpro) All the ligands were virtually screened, and 27 compounds were found to have high affinity with Mpro These compounds were assessed for drug-likeness analysis where two compounds were found to fit well for redocking studies Molecular docking, drug-likeness, X-Score, and toxicity analysis resulting in two lichen compounds, Calycin and Rhizocarpic acid with Mpro-inhibiting activity These compounds were finally subjected to molecular dynamics simulation to compare the dynamics behavior and stability of the Mpro after ligand binding The binding energy was calculated by MM-PBSA method to determine the intermolecular protein–ligand interactions Our results showed that two compounds; Calycin and Rhizocarpic acid had the binding free energy of − 4242 kJ mol/1 and − 5785 kJ mol/1 respectively as compared to reference X77 (− 9178 kJ mol/1) We concluded that Calycin and Rhizocarpic acid show considerable structural and pharmacological properties and they can be used as hit compounds to develop potential antiviral agents against SARS-CoV-2 These lichen compounds may be a suitable candidate for further experimental analysis

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Structure-based screening of novel lichen compounds against SARS Coronavirus main protease (Mpro) as potentials inhibitors of COVID-19.

A bioinformatic approach to identify core genome difference between Salmonella Pullorum and Salmonella Enteritidis In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking

Priyanka Sharma

Papers

In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking.

Molecular docking and molecular dynamics simulation approach to screen natural compounds for inhibition of Xanthomonas oryzae pv. Oryzae by targeting peptide deformylase.

Structure-based screening of novel lichen compounds against SARS Coronavirus main protease (Mpro) as potentials inhibitors of COVID-19.

A bioinformatic approach to identify core genome difference between Salmonella Pullorum and Salmonella Enteritidis In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking

In silico screening of potential antidiabetic phytochemicals from Phyllanthus emblica against therapeutic targets of type 2 diabetes