HI-164OV / Mariposa Health - LARVOL DELTA

Interrelated Mechanism by Which the Methide Quinone Celastrol, Obtained from the Roots of Tripterygium wilfordii, Inhibits Main Protease 3CL of COVID-19 and Acts as Superoxide Radical Scavenger. (PubMed, Int J Mol Sci) - "The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms...It proposes a covalent bond between the S(Cys145) amino acid thiolate and the celastrol A ring, assisted by proton transfers by His164 and His41 amino acids, and a π interaction from Met49 to the celastrol B ring. Specifically, celastrol possesses two moieties that are able to independently scavenge the superoxide radical: the carboxylic framework located at ring E, and the methide-quinone ring A. The latter captures the superoxide electron, releasing molecular oxygen, and is the feature of interest that correlates with the mechanism of COVID-19 inhibition. This unusual scavenging of the superoxide radical is described using density functional theory (DFT) methods, and is supported experimentally by cyclic voltammetry and X-ray diffraction."

Journal • Infectious Disease • Novel Coronavirus Disease • Ophthalmology • Respiratory Diseases

Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach. (PubMed, Futur J Pharm Sci) - "The chemical constituents from turmeric like cyclocurcumin and curcumin and from Andrographis paniculata like andrographolide and dihydroxy dimethoxy flavone are significantly binding with the active site of SARS CoV-2 main protease with Glide score more than - 6 when compared to the currently used drugs hydroxychloroquine (- 5.47) and nelfinavir (- 5.93). When compared to remdesivir (- 6.38), cyclocurcumin from turmeric is significantly more active...Main protease and the residues THR24, THR25, THR26, LEU27, SER46, MET49, HIE41, GLN189, ARG188, ASP187, MET165, HIE164, PHE181, and THR54 play a crucial role in binding with ligands. Based on in silico investigations, the chemical constituents from turmeric like cyclocurcumin and curcumin and from Andrographis paniculata like andrographolide and dihydroxy dimethoxy flavone, significantly binding with the active site of SARS CoV-2 main protease, may produce significant activity and be useful for further development."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Identification of tuna protein-derived peptides as potent SARS-CoV-2 inhibitors via molecular docking and molecular dynamic simulation. (PubMed, Food Chem) - "Molecular docking analysis revealed that E-M could interact with residues Thr190, Thr25, Thr26, Ala191, Leu50, Met165, Gln189, Glu166, His164, His41, Cys145, Gly143, and Asn119 of M via 11 conventional hydrogen bonds, 9 carbon hydrogen bonds, and one alkyl interaction. The formation of hydrogen bonds between peptide E-M and the residues Gly143 and Gln189 of M may play important roles in inhibiting the activity of M. Besides, E-M could bind with the residues His34, Phe28, Thr27, Ala36, Asp355, Glu37, Gln24, Ser19, Tyr83, and Tyr41 of ACE2. Hydrogen bonds and electrostatic interactions may play vital roles in blocking the receptor ACE2 binding with SARS-CoV-2."

Journal • Infectious Disease • Novel Coronavirus Disease

Fragment molecular orbital based interaction analyses on COVID-19 main protease - inhibitor N3 complex (PDB ID:6LU7). (PubMed, J Chem Inf Model) - "From the present FMO study, His41, His163, His164, and Glu166 were found to be the most important amino acid residues of Mpro in interacting with the inhibitor, mainly due to hydrogen bonding. A guideline for optimizations of the inhibitor molecule was suggested as well based on the FMO analysis."

Journal • Infectious Disease • Novel Coronavirus Disease

Identification of some novel oxazine substituted 9-anilinoacridines as SARS-CoV-2 inhibitors for COVID-19 by molecular docking, free energy calculation and molecular dynamics studies. (PubMed, J Biomol Struct Dyn) - "Compound A38 has the highest G-score (-7.83) when compared to all the standard compounds which are proposed for COVID-19 treatment such as ritonavir (-7.48), lopinavir (-6.94), nelfinavir (-5.93), hydroxychloroquine (-5.47) and mataquine (-5.37)...The residues GLN19, THR24, THR25, THR26, LEU27, HIE41, SER46, MET49, ASN119, ASN142, HIE164, MET165, ASP187, ARG188 and GLN189 of SARS-CoV-2 main protease play a crucial role in binding with ligands...Compound A38 was subjected to MD simulation at 100 ns to study the dynamic behaviour of protein-ligand complex. Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease

Chlorination versus hydroxylation selectivity mediated by the non-heme iron halogenase WelO5. (PubMed, Phys Chem Chem Phys) - "O2 activation leads to a Fe(iv)[double bond, length as m-dash]O moiety which adopts an equatorial conformation (in the plane consisting of His164, chloride and Fe atom), in contrast to axial conformation (perpendicular to the plane)...Notably, although Ser189 is vital for the selectivity of the enzyme, it is not part of the substrate binding pocket. Therefore, WelO5 serves as an excellent example how chemoselectivity can be achieved in directed evolution without the tedious redesign of the substrate binding pocket."

Journal

In silico study to evaluate the antiviral activity of novel structures against 3C-like protease of Novel Coronavirus (COVID-19) and SARS-CoV. (PubMed, Med Chem) - "These identified structures can be further assessed for their antiviral activity to combat SARS-CoV and COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease

Remdesivir (GS-5734) as a therapeutic option of 2019-nCOV main protease - in silico approach. (PubMed, J Biomol Struct Dyn) - "The 6LU7 residues, Cys145 and His164 are playing a significant role in replication and are essential for the survival of 2019-nCOV. Further, MD simulation analysis also confirmed, that these residues are forming H-bond with Remdesivir during 100 ns simulations run and found stable (∼99%) by RMSD and RMSF. Thus, present in silico study at molecular approaches suggest that, Remdesivir is a potent therapeutic inhibitor against 2019-nCoV."

Journal • Infectious Disease • Novel Coronavirus Disease

An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study. (PubMed, J Biomol Struct Dyn) - "All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under in vitro as well as in vivo conditions."

Journal • Infectious Disease • Novel Coronavirus Disease