Discovery of potential SARS-CoV 3CL protease inhibitors from approved antiviral drugs using: virtual screening, molecular docking, pharmacophore mapping evaluation and dynamics simulation.

The spread of corona-virus disease 2019 (COVID-19) has been faster than any other corona-viruses that have succeeded in crossing the animal-human barrier. This disease, caused by the severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2/2019-nCoV) posing a serious threat to global public health and local economies. There are three responsible for this disease; SARS-CoV-2, SARS-CoV and MERS-CoV. Whereas our goal is to test the affinity for a new class of compounds obtained from a hybridization of Chloroquine, Amodiaquine and Mefloquine with three targets SARS-CoV-2, SARS-CoV and MERS-CoV, in order to find new compounds as new inhibitors against Covid-19. In this work, we first used: the molecular docking/dynamics methods and ADME properties to study interaction and affinity between eight new compounds against three targets involved in the Covid-19. The results of the docking simulations and dynamics revealed that inhibitor of the malaria (Ligand 87) has an affinity to interact with SARS-CoV-2, SARS-CoV and MERS-CoV targets and they can be good inhibitors for treatment of Covid-19. Moreover, they give best affinity compared to the Remdesivir and Chloroquine and other clinical tests. The Pharmacokinetics was justified by means of lipophilicity and high coefficient of skin permeability. The in silico evaluation of ADME and drug-likeness revealed that L87 has higher absorption in the intestines with good bioavailability. However, an additional in vitro and/or in vivo experimental study should make it possible to verify the theoretical results obtained in silico.Communicated by Ramaswamy H. Sarma.

Potential inhibitors of angiotensin converting enzyme 2 receptor of COVID-19 by Corchorus olitorius Linn using docking, molecular dynamics, conceptual DFT investigation and pharmacophore mapping.

A novel coronavirus, previously designated 2019-nCoV, was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China, at the end of 2019. Our objective focuses on the in silico study to screen for an alternative drug that can block the activity of the angiotensin converting enzyme 2 (ACE2), which is a key protein in the physiology of Covid-19, necessary for the entry of the SARS-Cov-2 virus into the host's cells using natural compounds especially phenolic antioxidants, polyphenolics and pharmaceutically phytochemicals derived from the leaves of Corchorus olitorius Linn, appear to be very potential in controlling virus-induced infection. The results of the docking simulation revealed that méthyl-1,4,5-tri-O-caféoyl quinate has a stronger bond, high affinity and gives the best docking scores compared to, the co-crystallized inhibitor (PRD_002214) of the enzyme ACE2, chloroquine, hydroxychloroquine, captopril and simerprevir antiviral drugs. The ADMET properties, Pharmacokinetics and Medicinal Chemistry & P450 site of metabolism prediction, pharmacophore Mapper enzyme revealed that the compound méthyl-1,4,5-tri-O-caféoyl quinate generates a hypothesis which can be applied successfully in biological screening for further experiments. The novel MD computational technique study showed better conformational movements result for the méthyl-1,4,5-tri-O-caféoyl quinate-ACE2 docked complex. Therefore méthyl-1,4,5-tri-O-caféoyl quinate may be considered to be potential inhibitor of the main protease enzyme of virus, but need to be investigated in vivo and in vitro for further drug development process.Communicated by Ramaswamy H. Sarma.

In silico study the inhibition of angiotensin converting enzyme 2 receptor of COVID-19 by Ammoides verticillata components harvested from Western Algeria.

The objective of this present study is to focus on the in silico study to screen for an alternative drug that can block the activity of the angiotensin converting enzyme 2 (ACE2) as a receptor for SARS-CoV-2, potential therapeutic target of the COVID-19 virus using natural compounds (Isothymol, Thymol, Limonene, P-cymene and γ-terpinene) derived from the essential oil of the antiviral and antimicrobial plant Ammoides verticillata (Desf.) Briq. which is located in the occidental Algeria areas. This study reveals that Isothymol, a major component of this plant, gives the best docking scores, compared to, the co-crystallized inhibitor ß-D-mannose of the enzyme ACE2, to Captropil drug as good ACE2 inhibitor and to Chloroquine antiviral drug also involved in other mechanisms as inhibition of ACE2 cellular receptor. In silico (ADME), drug-likeness, PASS & P450 site of metabolism prediction, pharmacophore Mapper showed that the compound Isothymol has given a good tests results compared to the ß-D-mannose co-crystallized inhibitor, to Captopril and Chloroquine drugs. Also the other natural compounds gave good results. The Molecular Dynamics Simulation study showed good result for the Isotymol- ACE2 docked complex. This study revealed for the first time that Isothymol is a functional inhibitor of angiotensin converting enzyme 2 activity and the components of essential oils Ammoides verticillata can be used as potential inhibitors to the ACE2 receptor of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.