In Silico Screening and Design of Low Molecular Weight HIV-1 Inhibitors Interacting Cyclophilin-A That Assist HIV-1 Capsid Assembly

Posted: 14 Feb 2020

See all articles by T. Vani

T. Vani

Osmania University (OU)

Vijjulatha Manga

Osmania University (OU) - College of Science

Date Written: February 6, 2020

Abstract

The discovery of CypA inhibitor is of special interest in the treatment of immunological disorders since a network of protein vibrations has been identified in the enzyme cyclophilin-A (CypA) explicitly associated with its peptidyl-prolyl cis-trans isomerization activity. In this work we have characterized the significance of the Gly89-Pro90 peptide bond in the N-terminal domain of the capsid protein (CA). By utilizing several computational studies are thereby scrutinize the coalition of CypA into the capsid protein during the isomerization required distinctively for the HIV-1 infectious activity. The results reveal that CAN sequence preferentially His-87Ala-Gly-Pro-Ile-Ala-92 form the majority of the interactions with CypA residues. Interaction energies give support to ascertain protein-protein interactions in the CypA-CAN complex. In the current work, molecular modeling studies have been performed to develop a predictive Common Pharmacophore Hypothesis AARR, (CPH). The pharmacophore model has shown significant r2 and q2values of 0.923and 0.631 respectively. Molecular docking studies are carried out preferably to identify the binding interactions of these inhibitors with the receptor. New molecules are screened virtually employing CPH template. The results obtained from 3D-QSAR and docking studies assist in exploring potential inhibitors of Cyclophilin-A inhibitors.

Keywords: Human immunodeficiency virus type 1 (HIV-1); Cyclophillin A (CypA); Peptidyl-Prolyl Isomerase (PPIase); Capsid protein (CA); Pharmacophore Alignment and Scoring Engine (PHASE); N-terminal domain (NTD); Dissociation constant (Kd)

JEL Classification: y1

Suggested Citation

Vani, Tamalpakula and Manga, Vijjulatha, In Silico Screening and Design of Low Molecular Weight HIV-1 Inhibitors Interacting Cyclophilin-A That Assist HIV-1 Capsid Assembly (February 6, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3532896

Tamalpakula Vani (Contact Author)

Osmania University (OU) ( email )

Tarnaka
Hyderabad, Andhra Pradesh 500 007
India
8555928475 (Phone)

Vijjulatha Manga

Osmania University (OU) - College of Science ( email )

Hyderabad, Andhra Pradesh
India
9866845408 (Phone)

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