Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease
Infection by the emerging, potentially zoonotic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) presents a severe health hazard to humans and is often fatal. Given the lack of particular medicines against MERS-CoV, drug discovery studies are needed to bridge this knowledge gap. In this study...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2021-10-01
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| Series: | Dr. Sulaiman Al Habib Medical Journal |
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| Online Access: | https://journals.lww.com/10.2991/dsahmj.k.210921.001 |
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| author | Mahmoud Kandeel Byoung Kwon Park Mohamed A. Morsy Katharigatta N. Venugopala Kentaro Oh-hashi Mohammed Al-Nazawi Hyung-Joo Kwon |
| author_facet | Mahmoud Kandeel Byoung Kwon Park Mohamed A. Morsy Katharigatta N. Venugopala Kentaro Oh-hashi Mohammed Al-Nazawi Hyung-Joo Kwon |
| author_sort | Mahmoud Kandeel |
| collection | DOAJ |
| description | Infection by the emerging, potentially zoonotic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) presents a severe health hazard to humans and is often fatal. Given the lack of particular medicines against MERS-CoV, drug discovery studies are needed to bridge this knowledge gap. In this study, we introduce virtual screening-guided identification of MERS-CoV Papainlike Protease (PLpro)-binding drugs. After a two-step virtual screening method, enzyme assays and antiviral testing with a MERSCoV plaque reduction assay were used to further investigate the five compounds with the highest computational score. The top five screened compounds showed a 10.2-40% decrease in MERS-CoV PLpro activity. The top two compounds showed promising inhibition of MERS-CoV replication, reducing virus plaque formation by 30.6% and 24%. Compounds 1 and 4 in this study can be further modified to target binding with MERS-CoV PLpro active triad residues. Furthermore, the compounds produced stable interaction with the protein and protein conformation. With their reported inhibition of MERS-CoV enzyme and virus replication, supported by favorable absorption, distribution, metabolism, and excretion and toxicity profiles, the two reported benzimidazole and piperazine derivatives could be considered lead compounds against MERS-CoV. |
| format | Article |
| id | doaj-art-80dd0318c1e14ac19bb3f7f330e58d2a |
| institution | Kabale University |
| issn | 2666-819X 2590-3349 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Dr. Sulaiman Al Habib Medical Journal |
| spelling | doaj-art-80dd0318c1e14ac19bb3f7f330e58d2a2025-08-20T03:36:45ZengWolters Kluwer Medknow PublicationsDr. Sulaiman Al Habib Medical Journal2666-819X2590-33492021-10-013417918710.2991/dsahmj.k.210921.001Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like ProteaseMahmoud KandeelByoung Kwon ParkMohamed A. MorsyKatharigatta N. VenugopalaKentaro Oh-hashiMohammed Al-NazawiHyung-Joo KwonInfection by the emerging, potentially zoonotic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) presents a severe health hazard to humans and is often fatal. Given the lack of particular medicines against MERS-CoV, drug discovery studies are needed to bridge this knowledge gap. In this study, we introduce virtual screening-guided identification of MERS-CoV Papainlike Protease (PLpro)-binding drugs. After a two-step virtual screening method, enzyme assays and antiviral testing with a MERSCoV plaque reduction assay were used to further investigate the five compounds with the highest computational score. The top five screened compounds showed a 10.2-40% decrease in MERS-CoV PLpro activity. The top two compounds showed promising inhibition of MERS-CoV replication, reducing virus plaque formation by 30.6% and 24%. Compounds 1 and 4 in this study can be further modified to target binding with MERS-CoV PLpro active triad residues. Furthermore, the compounds produced stable interaction with the protein and protein conformation. With their reported inhibition of MERS-CoV enzyme and virus replication, supported by favorable absorption, distribution, metabolism, and excretion and toxicity profiles, the two reported benzimidazole and piperazine derivatives could be considered lead compounds against MERS-CoV.https://journals.lww.com/10.2991/dsahmj.k.210921.001mers-covpapain-like proteaseantiviral agentsvirtual screeningplaque |
| spellingShingle | Mahmoud Kandeel Byoung Kwon Park Mohamed A. Morsy Katharigatta N. Venugopala Kentaro Oh-hashi Mohammed Al-Nazawi Hyung-Joo Kwon Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease Dr. Sulaiman Al Habib Medical Journal mers-cov papain-like protease antiviral agents virtual screening plaque |
| title | Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease |
| title_full | Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease |
| title_fullStr | Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease |
| title_full_unstemmed | Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease |
| title_short | Virtual Screening and Inhibition of Middle East Respiratory Syndrome Coronavirus Replication by Targeting Papain-like Protease |
| title_sort | virtual screening and inhibition of middle east respiratory syndrome coronavirus replication by targeting papain like protease |
| topic | mers-cov papain-like protease antiviral agents virtual screening plaque |
| url | https://journals.lww.com/10.2991/dsahmj.k.210921.001 |
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