An Understanding of Coronavirus and exploring the Molecular Dynamics Simulations to Find Promising Candidates against the Mpro of nCoV to Combat the COVID-19: A Systematic Review

The first infection case of new coronavirus was reported at the end of 2019 and after then, the cases are reported in all nations in a very short period. Further, the regular news of mutations in the virus has made life restricted with appropriate behavior. To date, a new strain (Omicron and its new subvariant Omicron XE) has brought fear amongst us due to a higher trajectory of increase in the number of cases. The researchers thus started giving attention to this viral infection and discovering drug-like candidates to cure the infections. Finding a drug for any viral infection is not an easy task and takes plenty of time. Therefore, computational chemistry/bioinformatics is followed to get promising molecules against viral infection. Molecular dynamics (MD) simulations are being explored to get drug candidates in a short period. The molecules are screened via molecular docking, which provides preliminary information which can be further verified by MD simulations. To understand the change in structure, MD simulations generated several trajectories such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, and radius of gyration for the main protease (Mpro) of the new coronavirus (nCoV) in the presence of small molecules. Additionally, change in free energy for the formation of complex of Mpro of nCoV with the small molecule can be determined by applying molecular mechanics with generalized born and surface area solvation (MM-GBSA). Thus, the promising molecules can be further explored for clinical trials to combat COVID-19. Graphical

L-amino-acids as immunity booster against COVID-19: DFT, molecular docking and MD simulations.

There is great interest to explore the importance of different amino-acids on immunity of human. Immunity helps to protect us from the pathogenic infections. The amino-acids are being use to give energy and is also used as an important basic molecule for the making of cells, protecting cell and others. Still, a little information is known for their importance in the inhibition of main protease of SARS-CoV-2. As known, tens of billions of humans are infected due to the SARS-CoV-2 and about a million of deaths are reported due to it or COVID. As of now, no promising drug is available in the market to cure the patients from this infection. Even, the medicines beings used for the partial cure may have some side effects. Therefore, the focus is to explore the natural amino-acids against the Mpro of SARS-CoV-2 as using of amino-acids is not toxic to humans. In the present work, authors have studied the amino-acids using DFT calculations and then they were explored for their promising role in the inhibition of main protease of SARS-CoV-2 using molecular docking and molecular dynamics simulations. Out of the 20 amino-acids, arginine found to best against the main protease of SARS-CoV-2 using the molecular docking and the binding energy was -0.94 kcal/ mol. Further, molecular dynamics simulations for the main protease of SARS-CoV-2 with and without arginine was performed using the Amber and different thermodynamic parameters like ΔH and TΔS to get ΔG, comes out to be 2.74 kcal/mol. It is expected that arginine can boost the immunity.

An insight for the interaction of drugs (acyclovir/ganciclovir) with various ionic liquids: DFT calculations and molecular docking

Since December 2019, the humanity is in trouble due to the huge infection of SARS‐CoV‐2 and caused COVID‐19, named by WHO. Therefore, researchers and health care organizations are using the repurposing drugs against the infection by this new coronavirus. Acyclovir and ganciclovir are the drugs used in the cure of infection due to herpes virus so the impact of these drugs along with the designed ionic liquids individually as well as in combination against the Mpro of nCoV was investigated using molecular docking. The drugs {acyclovir (1) and ganciclovir (2)}, ionic liquids (A, B, and C), and their combinations (1‐A, 1‐B, 1‐C, 2‐A, 2‐B, and 2‐C) were studied using density functional theory (DFT) calculations via determining the different energies. These values are important to understand the formation of 1‐A, 1‐B, 1‐C, 2‐A, 2‐B, and 2‐C and are found to negative. Complexes formed by acyclovir with ILs (B and C) are more favorable due to less value of change in free energy. Further, 1 interacts with IL(C) and 2 interacts well with IL(A), and it is based on the calculated dipole moment of 1‐C and 2‐A, as 17.4 and 27.6, respectively. Therefore, it can be considered as more polar and more water soluble. Results revealed that complex 2‐A found to more stable than 1‐A and showed the best binding energy of −149 kcal/mol against the Mpro of nCoV. It indicates that the drug, ganciclovir (2) in presence of the IL(A) binds effectively with the Mpro of nCoV instead independently. [ABSTRACT FROM AUTHOR] Copyright of Journal of Physical Organic Chemistry is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

SARS-CoV-2 cell receptor gene ACE2 -mediated immunomodulation in breast cancer subtypes.

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has impacted the world severely. The binding of the SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) and its intake by the host cell is a necessary step for infection. ACE2 has garnered widespread therapeutic possibility as it is entry/interactive point for SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19) pandemic and providing a critical regulator for immune modulation in various disease. Patients with suffering from cancer always being on the verge of being immune compromised therefore gaining knowledge about how SARS-CoV-2 viruses affecting immune cells in human cancers will provides us new opportunities for preventing or treating virus-associated cancers. Despite COVID-19 pandemic got center stage at present time, however very little research being explores, which increase our knowledge in context with how SARS-CoV-2 infection affect cancer a cellular level. Therefore, in light of the ACE-2 as an important contributor of COVID-19 global, we analyzed correlation between ACE2 and tumor immune infiltration (TIL) level and the type markers of immune cells were investigated in breast cancer subtypes by using TIMER database. Our findings shed light on the immunomodulatory role of ACE2 in the luminal A subtype which may play crucial role in imparting therapeutic resistance in this cancer subtype.

DFT and docking studies of designed conjugates of noscapines & repurposing drugs: promising inhibitors of main protease of SARS-CoV-2 and falcipan-2.

First case of the present epidemic, coronavirus disease (COVID-19) is reported in the Wuhan, a city of the China and all the countries throughout the world are being affected. COVID-19 is named by World Health Organization and it stands for coronavirus disease-19. As on 27th October, 2020, 73,776,588 people around the world are infected. It is also known as SARS-CoV-2 infection. Till date, there is no promising drug or vaccine available in market to cure from this lethal infection. As the literature reported that noscapine a promising candidate to cure from malaria as well reported to be cough suppressant and anti-cancerous. In our previous work, a derivative of noscapine has shown potential behavior against the main protease of novel coronavirus or SARS-CoV-2. Based on the previous study, hybrid molecules based on noscapine and repurposing (antiviral) drugs were designed to target the main protease of novel coronavirus and falcipan-2 using molecular docking. It is proposed that the designed hydrids or conjugates may have promising antiviral property i.e. against the main protease of novel coronavirus and falcipan-2. The designed molecules were thoroughly studied by DFT and different thermodynamic parameters were determined. Further, infrared and Raman spectra of the designed hybrid molecules were determined and studied. Communicated by Ramaswamy H. Sarma.

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation.

Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to man as well as surface to man . In the present work, in silico approach was followed to find potential molecule to control this infection. Authors have screened more than one million molecules available in the ZINC database and taken the best two compounds based on binding energy score. These lead molecules were further studied through docking against the main protease of SARS-CoV-2. Then, molecular dynamics simulations of the main protease with and without screened compounds were performed at room temperature to determine the thermodynamic parameters to understand the inhibition. Further, molecular dynamics simulations at different temperatures were performed to understand the efficiency of the inhibition of the main protease in the presence of the screened compounds. Change in energy for the formation of the complexes between the main protease of novel coronavirus and ZINC20601870 as well ZINC00793735 at room temperature was determined on applying MM-GBSA calculations. Docking and molecular dynamics simulations showed their antiviral potential and may inhibit viral replication experimentally. Communicated by Ramaswamy H. Sarma.

Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures.

The current outbreak of a novel coronavirus, named as SARS-CoV-2 causing COVID-19 occurred in 2019, is in dire need of finding potential therapeutic agents. Recently, ongoing viral epidemic due to coronavirus (SARS-CoV-2) primarily affected mainland China that now threatened to spread to populations in most countries of the world. In spite of this, there is currently no antiviral drug/ vaccine available against coronavirus infection, COVID-19. In the present study, computer-aided drug design-based screening to find out promising inhibitors against the coronavirus (SARS-CoV-2) leads to infection, COVID-19. The lead therapeutic molecule was investigated through docking and molecular dynamics simulations. In this, binding affinity of noscapines(23B)-protease of SARS-CoV-2 complex was evaluated through MD simulations at different temperatures. Our research group has established that noscapine is a chemotherapeutic agent for the treatment of drug resistant cancers; however, noscapine was also being used as anti-malarial, anti-stroke and cough-suppressant. This study suggests for the first time that noscapine exerts its antiviral effects by inhibiting viral protein synthesis.