Carbon fullerene and nanotube are probable binders to multiple targets of SARS-CoV-2: Insights from computational modeling and molecular dynamic simulation studies.

The present study aimed to predict the binding potential of carbon nanotube and nano fullerene towards multiple targets of SARS-CoV-2. Based on the virulent functions, the spike glycoprotein, RNA-dependent RNA polymerase, main protease, papain-like protease, and RNA binding domain of the nucleocapsid proteins of SARS-CoV-2 were prioritized as the molecular targets and their three-dimensional (3D) structures were retrieved from the Protein Data Bank. The 3D structures of carbon nanotubes and nano-fullerene were computationally modeled, and the binding potential of these nanoparticles to the selected molecular targets was predicted by molecular docking and molecular dynamic (MD) simulations. The drug-likeness and pharmacokinetic features of the lead molecules were computationally predicted. The current study suggested that carbon fullerene and nanotube demonstrated significant binding towards the prioritized multi-targets of SARS-CoV-2. Interestingly, carbon nanotube showed better interaction with these targets when compared to carbon fullerene. MD simulation studies clearly showed that the interaction of nanoparticles and selected targets possessed stability and conformational changes. This study revealed that carbon nanotubes and fullerene are probably used as effectual binders to multiple targets of SARS-CoV-2, and the study offers insights into the experimental validation and highlights the relevance of utilizing carbon nanomaterials as a therapeutic remedy against COVID-19.

Structural insights on the interaction potential of natural leads against major protein targets of SARS-CoV-2: Molecular modelling, docking and dynamic simulation studies.

Though significant efforts are in progress for developing drugs and vaccines against COVID-19, limited therapeutic agents are available currently. Thus, it is essential to undertake COVID-19 research and to identify therapeutic interventions in which computational modeling and virtual screening of lead molecules provide significant insights. The present study aimed to predict the interaction potential of natural lead molecules against prospective protein targets of SARS-CoV-2 by molecular modeling, docking, and dynamic simulation. Based on the literature survey and database search, fourteen molecular targets were selected and the three targets which lack the native structures were computationally modeled. The drug-likeliness and pharmacokinetic features of ninety-two natural molecules were predicted. Four lead molecules with ideal drug-likeliness and pharmacokinetic properties were selected and docked against fourteen targets, and their binding energies were compared with the binding energy of the interaction between Chloroquine and Hydroxychloroquine to their usual targets. The stabilities of selected docked complexes were confirmed by MD simulation and energy calculations. Four natural molecules demonstrated profound binding to most of the prioritized targets, especially, Hyoscyamine and Tamaridone to spike glycoprotein and Rotiorinol-C and Scutifoliamide-A to replicase polyprotein-1ab main protease of SARS-CoV-2 showed better binding energy, conformational and dynamic stabilities compared to the binding energy of Chloroquine and its usual target glutathione-S-transferase. The aforementioned lead molecules can be used to develop novel therapeutic agents towards the protein targets of SARS-CoV-2, and the study provides significant insight for structure-based drug development against COVID-19.

Structural and molecular basis of the interaction mechanism of selected drugs towards multiple targets of SARS-CoV-2 by molecular docking and dynamic simulation studies- deciphering the scope of repurposed drugs.

The repurposing of FDA approved drugs is presently receiving attention for COVID-19 drug discovery. Previous studies revealed the binding potential of several FDA-approved drugs towards specific targets of SARS-CoV-2; however, limited studies are focused on the structural and molecular basis of interaction of these drugs towards multiple targets of SARS-CoV-2. The present study aimed to predict the binding potential of six FDA drugs towards fifteen protein targets of SARS-CoV-2 and propose the structural and molecular basis of the interaction by molecular docking and dynamic simulation. Based on the literature survey, fifteen potential targets of SARS-CoV-2, and six FDA drugs (Chloroquine, Hydroxychloroquine, Favipiravir, Lopinavir, Remdesivir, and Ritonavir) were selected. The binding potential of individual drug towards the selected targets was predicted by molecular docking in comparison with the binding of the same drugs with their usual targets. The stabilities of the best-docked conformations were confirmed by molecular dynamic simulation and energy calculations. Among the selected drugs, Ritonavir and Lopinavir showed better binding towards the prioritized targets with minimum binding energy (kcal/mol), cluster-RMS, number of interacting residues, and stabilizing forces when compared with the binding of Chloroquine, Favipiravir, and Hydroxychloroquine, later drugs demonstrated better binding when compared to the binding with their usual targets. Remdesvir showed better binding to the prioritized targets in comparison with the binding of Chloroquine, Favipiravir, and Hydroxychloroquine, but showed lesser binding potential when compared to the interaction between Ritonavir and Lopinavir and the prioritized targets. The structural and molecular basis of interactions suggest that the FDA drugs can be repurposed towards multiple targets of SARS-CoV-2, and the present computational models provide insights on the scope of repurposed drugs against COVID-19.

Elucidating the microscopic and computational techniques to study the structure and pathology of SARS-CoVs.

Severe Acute Respiratory Syndrome Coronaviruses (SARS-CoVs), causative of major outbreaks in the past two decades, has claimed many lives all over the world. The virus effectively spreads through saliva aerosols or nasal discharge from an infected person. Currently, no specific vaccines or treatments exist for coronavirus; however, several attempts are being made to develop possible treatments. Hence, it is important to study the viral structure and life cycle to understand its functionality, activity, and infectious nature. Further, such studies can aid in the development of vaccinations against this virus. Microscopy plays an important role in examining the structure and topology of the virus as well as pathogenesis in infected host cells. This review deals with different microscopy techniques including electron microscopy, atomic force microscopy, fluorescence microscopy as well as computational methods to elucidate various prospects of this life-threatening virus.