Allostery and Missense Mutations as Intermittently Linked Promising Aspects of Modern Computational Drug Discovery DOI Creative Commons
Özlem Taştan Bishop, Thommas M. Musyoka, Victor Barozi

et al.

Journal of Molecular Biology, Journal Year: 2022, Volume and Issue: 434(17), P. 167610 - 167610

Published: April 28, 2022

Drug research and development is a multidisciplinary field with its own successes. Yet, given the complexity of process, it also faces challenges over long stages even includes those that develop once drug marketed, i.e. toxicity resistance. Better success can be achieved via well designed criteria in early stages. Here, we introduce concepts allostery missense mutations, argue incorporation these two intermittently linked biological phenomena into computational discovery would help to reduce attrition risk later process. We discuss individual or concert mechanisms actions mutations allostery. Design allosteric drugs challenging compared orthosteric drugs, yet they have been gaining popularity recent years as alternative systems for therapeutic regulation proteins an action-at-a-distance mode non-invasive mechanisms. propose easy-to-apply protocol which considers mutation effect, detail three case studies focusing on (1) analysis effect related isoniazid resistance tuberculosis; (2) identification cryptic pocket presence falcipain-2 malarial target; (3) deciphering effects SARS-CoV-2 evolutionary potential modulator changes communication paths.

Language: Английский

Transfer Learning Towards Predicting Viral Missense Mutations: A Case Study on SARS-CoV-2 DOI Creative Commons
S. Govender,

Emily L Morgan,

Rabelani Ramahala

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Allosteric Hotspots in the Main Protease of SARS-CoV-2 DOI
Léonie Strömich, Nan Wu, Mauricio Barahona

et al.

Journal of Molecular Biology, Journal Year: 2022, Volume and Issue: 434(17), P. 167748 - 167748

Published: July 16, 2022

Language: Английский

Citations

18
Antiviral activities of natural compounds and ionic liquids to inhibit the Mpro of SARS-CoV-2: a computational approach DOI Creative Commons
Kandhan Palanisamy, S. M. Esther Rubavathy, Muthuramalingam Prakash

et al.

RSC Advances, Journal Year: 2022, Volume and Issue: 12(6), P. 3687 - 3695

Published: Jan. 1, 2022

The recalcitrant spread of the COVID-19 pandemic produced by novel coronavirus SARS-CoV-2 is one most destructive occurrences in history. Despite availability several effective vaccinations and their widespread use, this line immunization often faces questions about its long-term efficacy. Since coronaviruses rapidly change, multiple variants have emerged around world. Therefore, finding a new target-based medication became priority to prevent control infections. main protease (Mpro) salient enzyme that plays vital role viral replication, making it fascinating therapeutic target for SARS-CoV-2. We screened 0.2 million natural products against Mpro using Universal Natural Product Database (UNPD). As well, we studied ionic liquids (ILs) on structural stabilization Mpro. Cholinium-based ILs are biocompatible used variety biomedical applications. Molecular docking was employed initial screening To predict drug-likeness features lead compounds, calculated ADMET properties. performed MD simulations selected complexes based outcomes. Using MM/PBSA approaches, conclude compounds NP-Hit2 (-25.6 kcal mol-1) NP-Hit3 (-25.3 show stronger binding affinity with hotspot residues Thr25, Leu27, His41, Met49, Cys145, Met165, Gln189 strongly interacted compounds. Furthermore, naproxenate, ketoprofenate, geranate, cholinium-based interact these antimicrobial Our findings will aid development inhibitors.

Language: Английский

Citations

17
Dynamic allostery highlights the evolutionary differences between the CoV-1 and CoV-2 main proteases DOI Creative Commons
Paul Campitelli, Lu Jin, S. Banu Ozkan

et al.

Biophysical Journal, Journal Year: 2022, Volume and Issue: 121(8), P. 1483 - 1492

Published: March 15, 2022

Language: Английский

Citations

17
Allostery and Missense Mutations as Intermittently Linked Promising Aspects of Modern Computational Drug Discovery DOI Creative Commons
Özlem Taştan Bishop, Thommas M. Musyoka, Victor Barozi

et al.

Journal of Molecular Biology, Journal Year: 2022, Volume and Issue: 434(17), P. 167610 - 167610

Published: April 28, 2022

Drug research and development is a multidisciplinary field with its own successes. Yet, given the complexity of process, it also faces challenges over long stages even includes those that develop once drug marketed, i.e. toxicity resistance. Better success can be achieved via well designed criteria in early stages. Here, we introduce concepts allostery missense mutations, argue incorporation these two intermittently linked biological phenomena into computational discovery would help to reduce attrition risk later process. We discuss individual or concert mechanisms actions mutations allostery. Design allosteric drugs challenging compared orthosteric drugs, yet they have been gaining popularity recent years as alternative systems for therapeutic regulation proteins an action-at-a-distance mode non-invasive mechanisms. propose easy-to-apply protocol which considers mutation effect, detail three case studies focusing on (1) analysis effect related isoniazid resistance tuberculosis; (2) identification cryptic pocket presence falcipain-2 malarial target; (3) deciphering effects SARS-CoV-2 evolutionary potential modulator changes communication paths.

Language: Английский

Citations

17