Repurposing of renin inhibitors as SARS-COV-2 main protease inhibitors: A computational study

<a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (Mpro) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (Mpros) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (Mpro) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a>

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Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel in Silico Method

10.26434/chemrxiv.12248561.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Milan Sencanski ◽

Vladimir Perovic ◽

Snezana Pajovic ◽

Miroslav Adzic ◽

Slobodan Paessler ◽

...

Keyword(s):

Protease Inhibitors ◽

In Silico ◽

Drug Target ◽

Transmission Rate ◽

Experimental Testing ◽

Drug Repurposing ◽

Global Public Health ◽

Main Protease ◽

Additional Approach ◽

Drugbank Database

The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening (VS) protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the ISM applied for Small Molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing.

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Synthesis, characterization, and computational study of copper bipyridine complex [Cu (C18H24N2) (NO3)2] to explore its functional properties

Zeitschrift für Naturforschung C ◽

10.1515/znc-2021-0248 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Saleh S. Alarfaji ◽

Sajjad Hussain ◽

Abdullah G. Al-Sehemi ◽

Shabbir Muhammad ◽

Islam Ullah Khan ◽

...

Keyword(s):

Computational Study ◽

Coordination Complexes ◽

Mononuclear Complex ◽

Orthorhombic Space Group ◽

Main Protease ◽

Analysis Technique ◽

Infra Red ◽

Chemical Techniques ◽

The Stability ◽

Single Crystal Analysis

Abstract In the present study, copper (II) complex of 4, 4′-di-tert-butyl-2,2′-bipyridine [Cu (C18H24N2) (NO3)2], 1 is investigated through its synthesis and characterization using elemental analysis technique, infra-red spectroscopy, and single-crystal analysis. The compound 1 crystallizes in orthorhombic space group P212121. The copper atom in the mononuclear complex is hexa coordinated through two nitrogen and four oxygen atoms from bipyridine ligand and nitrate ligands. The thermal analysis depicts the stability of the entitled compound up to 170 °C, and the decomposition takes place in different steps between 170 and 1000 °C. Furthermore, quantum chemical techniques are used to study optoelectronic, nonlinear optical, and therapeutic bioactivity. The values of isotropic and anisotropic linear polarizabilities of compound 1 are calculated as 41.65 × 10−24 and 23.02 × 10−24 esu, respectively. Likewise, the static hyperpolarizability is calculated as 47.92 × 10−36 esu using M06 functional compared with para-nitroaniline (p-NA) and found several times larger than p-NA. Furthermore, the antiviral potential of compound 1 is studied using molecular docking technique where intermolecular interactions are checked between the entitled compound and two crucial proteins of SARS-CoV-2 (COVID-19). Our investigation indicated that compound 1 interacts more vigorously to spike protein than main protease (MPro) due to its better binding energy of −9.60 kcal/mol compared with −9.10 kcal/mol of MPro. Our current study anticipated that the above-entitled coordination complexes could be potential candidates for optoelectronic properties and their biological activity.

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