Structure-based discovery of F.religiosa phytochemicals as potential inhibitors against Monkeypox(mpox)viral protein  

作　　者：Ranjan K.Mohapatra Ahmed Mahal Pranab K.Mohapatra Ashish K.Sarangi Snehasish Mishra Meshari A.Alsuwat Nada N.Alshehri Sozan M.Abdelkhalig Mohammed Garout Mohammed Aljeldah Ahmad A.Alshehri Ahmed Saif Mohammed Abdulrahman Alshahrani Ali S.Alqahtani Yahya A.Almutawif Hamza M.A.Eid Faisal M Albaqami Mohnad Abdalla Ali A.Rabaan 

机构地区：[1]Department of Chemistry,Government College of Engineering,Keonjhar 758002,Odisha,India [2]Department of Medical Biochemical Analysis,College of Health Technology,Cihan University–Erbil,Erbil,Kurdistan Region,Iraq [3]Department of Chemistry,CV Raman Global University,Bhubaneswar,Odisha,India [4]Department of Chemistry,School of Applied Sciences,Centurion University of Technology and Management,Balangir,Odisha,India [5]School of Biotechnology,Campus-11,KIIT Deemed-to-be-University,Bhubaneswar 751024,Odisha,India [6]Clinical Laboratory Sciences Department,College of Applied Medical Sciences,Taif University,Al-Taif 21974,Saudi Arabia [7]Internal Medicine Department,King Khalid University Medical City,College of Medicine,Abha 61481,Saudi Arabia [8]Department of Basic Medical Sciences,College of Medicine,AlMaarefa University,Riyadh,Saudi Arabia [9]Department of Community Medicine and Health Care for Pilgrims,Faculty of Medicine,Umm Al-Qura University,Makkah 21955,Saudi Arabia [10]Department of Clinical Laboratory Sciences,College of Applied Medical Sciences,University of Hafr Al Batin,Hafr Al Batin 39831,Saudi Arabia [11]Department of Clinical Laboratory Sciences,Faculty of Applied Medical Sciences,Najran University,Najran 61441,Saudi Arabia [12]Department of Medical Laboratory Sciences,Faculty of Applied Medical Sciences,King Khalid University,Abha 61481,Saudi Arabia [13]mDepartment of Medical Laboratories Technology,College of Applied Medical Sciences,Taibah University,Madinah 41411,Saudi Arabia [14]Biology Department,College of Science,Islamic University of Madinah,Madinah 42351,Saudi Arabia [15]Pediatric Research Institute,Children’s Hospital Affiliated to Shandong University,Jinan,Shandong 250022,China [16]Molecular Diagnostic Laboratory,Johns Hopkins Aramco Healthcare,Dhahran 31311,Saudi Arabia [17]College of Medicine,Alfaisal University,Riyadh 11533,Saudi Arabia [18]Department of Public Health and Nutrition,The University of Haripur,Haripur 22610,Pakistan

出　　处：《Journal of Biosafety and Biosecurity》2024年第3期157-169,共13页生物安全和生物安保杂志（英文）

摘　　要：Outbreaks of Monkeypox(mpox)in over 100 non-endemic countries in 2022 represented a serious global health concern.Once a neglected disease,mpox has become a global public health issue.A42R profilinlike protein from mpox(PDB ID:4QWO)represents a potential new lead for drug development and may interact with various synthetic and natural compounds.In this report,the interaction of A42R profilinlike protein with six phytochemicals found in the medicinal plant Ficus religiosa(abundant in India)was examined.Based on the predicted and compared protein–ligand binding energies,biological properties,IC_(50) values and toxicity,two compounds,kaempferol(C-1)and piperine(C-4),were selected.ADMET characteristics and quantitative structure–activity relationship(QSAR)of these two compounds were determined,and molecular dynamics(MD)simulations were performed.In silico examination of the kaempferol(C-1)and piperine(C-4)interactions with A42R profilin-like protein gave best-pose ligandbinding energies of–6.98 and–5.57 kcal/mol,respectively.The predicted IC_(50) of C-1 was 7.63 lM and 82 lM for C-4.Toxicity data indicated that kaempferol and piperine are non-mutagenic,and the QSAR data revealed that piperlongumine(5.92)and piperine(5.25)had higher log P values than the other compounds examined.MD simulations of A42R profilin-like protein in complex with C-1 and C-4 were performed to examine the stability of the ligand–protein interactions.As/C and C-4 showed the highest affinity and activities,they may be suitable lead candidates for developing mpox therapeutic drugs.This study should facilitate discovering and synthesizing innovative therapeutics to address other infectious diseases.

关 键 词：MONKEYPOX Mpox PHYTOCHEMICAL Molecular docking MD simulation ADMET QSAR 

分 类 号：R511[医药卫生—内科学]