Ivermectin as a potential drug for treatment of COVID-19: an in-sync review with clinical and computational attributes

Harpinder Kaur, Nishant Shekhar, Saurabh Sharma, Phulen Sarma, Ajay Prakash, Bikash Medhi, Harpinder Kaur, Nishant Shekhar, Saurabh Sharma, Phulen Sarma, Ajay Prakash, Bikash Medhi

Abstract

Introduction: COVID-19 cases are on surge; however, there is no efficient treatment or vaccine that can be used for its management. Numerous clinical trials are being reviewed for use of different drugs, biologics, and vaccines in COVID-19. A much empirical approach will be to repurpose existing drugs for which pharmacokinetic and safety data are available, because this will facilitate the process of drug development. The article discusses the evidence available for the use of Ivermectin, an anti-parasitic drug with antiviral properties, in COVID-19.

Methods: A rational review of the drugs was carried out utilizing their clinically significant attributes. A more thorough understanding was met by virtual embodiment of the drug structure and realizable viral targets using artificial intelligence (AI)-based and molecular dynamics (MD)-simulation-based study.

Conclusion: Certain studies have highlighted the significance of ivermectin in COVID-19; however, it requires evidences from more Randomised Controlled Trials (RCTs) and dose- response studies to support its use. In silico-based analysis of ivermectin's molecular interaction specificity using AI and classical mechanics simulation-based methods indicates positive interaction of ivermectin with viral protein targets, which is leading for SARS-CoV 2 N-protein NTD (nucleocapsid protein N-terminal domain).

Keywords: COVID-19; Ivermectin; SARS-CoV-2; Treatment.

Figures

Fig. 1
Fig. 1
Mechanism of actions of ivermectin
Fig. 2
Fig. 2
C-alpha RMSD of different SARS-CoV-2 protein targets representing contact with Ivermectin in 100 ns simulation
Fig. 3
Fig. 3
2D contact with the protein targets of ivermectin with the interaction strength represented with adjacent active site residues (magenta continuous line: H-bond with Cα of protein; magenta dotted line: H-bond with side chain groups; green residue: hydrophobic; blue residue: polar residue, grey dots: solvent exposure) a N -protein contact with Ivermectin, b S1-RBD contact with Ivermectin, c S2 fusion peptide contact with Ivermectin, d CL protease contact with Ivermectin
Fig. 4
Fig. 4
Ivermectin contact profile with SARS CoV-2 proteins a S1-RBD, b S2 fusion domain, c N protein NTD and d CL protease
Fig. 5
Fig. 5
The 3D representation of ivermectin showing interaction points of ivermectin molecule in final bound trajectory frames with: a S1-RBD, b S2 fusion domain, c N protein NTD and d main protease (Yellow dotted line: H-bond, orange dotted line: indistinct weak interaction)

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