Examining pharmacodynamic and pharmacokinetic properties of eleven analogues of saquinavir for HIV protease inhibition

Jayaswal, Amit; Mishra, Hirdyesh; Mishra, Ankita; Shah, Kavita

doi:10.1007/s00705-019-04153-9

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…Saquinavir is a specific inhibitor drug for HIV protease. Jayaswal et al 34 carried out an in silico study with modified Saquinavir structures to test the interaction with the HIV protease active site, with the aim of finding structures that present better binding energy than Saquinavir. Khadim et al 33 conducted an in silico study of the interaction of SARS-Cov-2 main protease (Mpro) with anti-HIV drugs.…”

Section: Resultsmentioning

confidence: 99%

Interaction of Drug Candidates with Various SARS-CoV-2 Receptors: An in Silico Study to Combat COVID-19

et al. 2020

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The world is currently facing the COVID-19 pandemic caused by the SARS-CoV-2 virus. The pandemic is causing the death of people around the world, and public and social health measures to slow or prevent the spread of COVID-19 are being implemented with the involvement of all members of society. Research institutions are accelerating the discovery of vaccines and therapies for COVID-19. In this work, molecular docking was used to study (in silico) the interaction of 24 ligands, divided into four groups, with four SARS-CoV-2 receptors, Nsp9 replicase, main protease (Mpro), NSP15 endoribonuclease, and spike protein (S-protein) interacting with human ACE2. The results showed that the antimalarial drug Metaquine and anti-HIV antiretroviral Saquinavir interacted with all the studied receptors, indicating that they are potential candidates for multitarget drugs for COVID-19.

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Section: Resultsmentioning

confidence: 99%

Interaction of Drug Candidates with Various SARS-CoV-2 Receptors: An in Silico Study to Combat COVID-19

et al. 2020

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“…On the other hand, the importance of crossing the blood–brain barrier (BBB) for an anti-HIV drug remains unclear, since anti-HIV drugs do not reside on the brain side of the BBB and prefer to remain on the blood side. However, ineffective penetration of anti-HIV drugs into the brain can trigger HIV recurrence due to the remaining reservoirs in the central nervous system (CNS) and can cause HIV-associated neurocognitive disorders [ 54 , 55 , 56 ]. In silico pharmacokinetic studies employed for H-2, H-6, H-32, H-39, H-62, H-64, H-86, H-189, and H-201 indicated that all of them possessed moderate drug-likeness profiles with appropriate CIQPlogS and QPlogPo/w values.…”

Section: Discussionmentioning

confidence: 99%

Identification of New L-Heptanoylphosphatidyl Inositol Pentakisphosphate Derivatives Targeting the Interaction with HIV-1 Gag by Molecular Modelling Studies

et al. 2022

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The HIV-1 Gag protein binds to the host cell membrane and assembles into immature particles. Then, in the course of immature virion budding, activated protease cleaves Gag into its main components: MA, CA, NC, and p6 proteins. The highly basic residues of MA predominantly interact with the acidic head of phosphatidyl-inositol-4,5-bisphosphate (PI(4,5)P2) inserted into the membrane. Our research group developed L-Heptanoylphosphatidyl Inositol Pentakisphosphate (L-HIPPO) and previously confirmed that this compound bound to the MA more strongly than PI(4,5)P2 and inositol hexakisphosphate (IP6) did. Therefore, herein we rationally designed eight new L-HIPPO derivatives based on the fact that the most changeable parts of L-HIPPO were two acyl chains. After that, we employed molecular docking for eight compounds via Maestro software using high-resolution crystal structures of MA in complex with IP6 (PDB IDs: 7E1I, 7E1J, and 7E1K), which were recently elucidated by our research group. The most promising docking scores were obtained with benzene-inserted compounds. Thus, we generated a library containing 213 new aromatic group-inserted L-HIPPO derivatives and performed the same molecular docking procedure. According to the results, we determined the nine new L-HIPPO derivatives most effectively binding to the MA with the most favorable scoring functions and pharmacokinetic properties for further exploration.

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Environmentally benign synthesis of unsymmetrical ureas and their evaluation as potential HIV-1 protease inhibitors via a computational approach

et al. 2023

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Examining pharmacodynamic and pharmacokinetic properties of eleven analogues of saquinavir for HIV protease inhibition

Cited by 5 publications

References 18 publications

Interaction of Drug Candidates with Various SARS-CoV-2 Receptors: An in Silico Study to Combat COVID-19

Interaction of Drug Candidates with Various SARS-CoV-2 Receptors: An in Silico Study to Combat COVID-19

Identification of New L-Heptanoylphosphatidyl Inositol Pentakisphosphate Derivatives Targeting the Interaction with HIV-1 Gag by Molecular Modelling Studies

Environmentally benign synthesis of unsymmetrical ureas and their evaluation as potential HIV-1 protease inhibitors via a computational approach

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