Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach

被引：7

作者：

Al Mashud, Md. Abdullah ^{[1
]}

Kumer, Ajoy ^{[2
]}

Mukerjee, Nobendu ^{[3
,4
]}

Chandro, Akhel ^{[5
]}

Maitra, Swastika ^{[6
]}

Chakma, Unesco ^{[2
,7
]}

Dey, Abhijit ^{[8
]}

Akash, Shopnil ^{[9
]}

Alexiou, Athanasiosis ^{[10
,11
]}

Khan, Azmat Ali ^{[12
]}

Alanazi, Amer M. ^{[12
]}

Ghosh, Arabinda ^{[13
]}

Chen, Kow-Tong ^{[14
,15
]}

Sharma, Rohit ^{[16
]}

机构：

[1] Islamic Univ, Dept Elect & Elect Engn, Biophys & Biomed Res Lab, Kushtia, Bangladesh

[2] European Univ Bangladesh, Dept Chem, Lab Computat Res Drug Design & Mat Sci, Dhaka, Bangladesh

[3] West Bengal State Univ, Dept Microbiol, Kolkata, W Bengal, India

[4] Novel Global Community Educ Fdn, Dept Hlth Sci, Habersham, NSW, Australia

[5] Sher E Bangla Agr Univ, Fac Anim Sci & Vet Med, Dept Poultry Sci, Dhaka, Bangladesh

[6] Adamas Univ, Dept Microbiol, Kolkata, W Bengal, India

[7] Southeast Univ, Sch Elect Sci & Engn, Nanjing, Peoples R China

[8] Presidency Univ, Dept Life Sci, Kolkata, W Bengal, India

[9] Daffodil Int Univ, Dept Pharm, Dhaka, Bangladesh

[10] Novel Global Community Educ Fdn, Dept Sci & Engn, Habersham, NSW, Australia

[11] AFNP Med, Dept Neurosci, Vienna, Austria

[12] King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, Pharmaceut Biotechnol Lab, Riyadh, Saudi Arabia

[13] Gauhati Univ, Dept Bot, Microbiol Div, Gauhati, Assam, India

[14] Tainan Municipal Hosp, Dept Occupat Med, Show Chwan Med Care Corp, Tainan, Taiwan

[15] Natl Cheng Kung Univ, Coll Med, Dept Publ Hlth, Tainan, Taiwan

[16] Banaras Hindu Univ, Inst Med Sci, Fac Ayurveda, Dept Rasa Shastra & Bhaishajya Kalpana, Varanasi, Uttar Pradesh, India

来源：

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY | 2023年 / 13卷

关键词：

Monkeypox virus; Marburg virus; drug development; O-rhamnosides; Kaempferol-o-rhamnosides; admet; molecular docking; molecular dynamics simulations; DISEASE; UGANDA; PREDICTION; OUTBREAK; DOCKING;

D O I：

10.3389/fcimb.2023.1188763

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study's primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses.

引用

页数：17