RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic

Tian, Lei; Qiang, Taotao; Liang, Chengyuan; Ren, Xiaodong; Jia, Minyi; Zhang, Jiayun; Li, Jingyi; Wan, Minge; YuWen, Xin; Li, Han; Cao, Wenqiang; Liu, Hong

doi:10.1016/j.ejmech.2021.113201

Cited by 166 publications

(174 citation statements)

References 183 publications

(132 reference statements)

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“…The binding energy of the hit molecules ( 2 - 22 ) have been compared with the co-crystallized ligand remdesivir ( 1 , Table 1 , Entry 1). Further, these hits ( 2 - 22 ) have been found with better binding energy as compared to other promising RdRp inhibitors such as ribavirin ( 23 ), penciclovir ( 24 ), favipravir ( 25 ), [36] molnupiravir ( 26 ) and sofosbuvir ( 27 ) [37] . Total twenty-one identified macrocyclic hits have been found to possess binding energy lesser than -12.5 Kcal/mol and presented in Table 1 and their 2D-possess with the formed interactions have been presented in Figure S1-S4 (see supporting informartion).…”

Section: Resultsmentioning

confidence: 99%

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

Nagar

Gajjar

Dhameliya

2021

Journal of Molecular Structure

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Severe acute respiratory syndrome has relapsed recently as novel coronavirus causing a life threat to the entire world in the absence of an effective therapy. To hamper the replication of the deadly SARS CoV-2 inside the host cells, systematic in silico virtual screening of total 267,324 ligands from Asinex EliteSynergy and BioDesign libraries has been performed using AutoDock Vina against RdRp. The molecular modeling studies revealed the identification of twenty-one macrocyclic hits ( 2 - 22 ) with better binding energy than remdesivir ( 1 ), marketed SARS CoV-2 inhibitor. Further, the analysis using rules for drug-likeness and their ADMET profile revealed the candidature of these hits due to superior oral bioavailability and druggability. Further, the MD simulation studies of top two hits ( 2 and 3 ) performed using GROMACS 2020.1 for 10 ns revealed their stability into the docked complexes. These results provide an important breakthrough in the design of macrocyclic hits as SARS CoV-2 RNA replicase inhibitor.

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Section: Resultsmentioning

confidence: 99%

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

Nagar

Gajjar

Dhameliya

2021

Journal of Molecular Structure

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“…RdRp inhibitors have already been commonly used in the treatment of HIV, Zika virus, and Ebola infections. Since SARS-CoV-2 is also an RNA virus, RdRp could be effective against SARS-CoV-2 [42,43].…”

Section: Understanding the Mechanism And Structure Of Sars-cov-2mentioning

confidence: 99%

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

Ertürk

Şahin

et al. 2021

Molecules

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Since December 2019, humanity has faced an important global threat. Many studies have been published on the origin, structure, and mechanism of action of the SARS-CoV-2 virus and the treatment of its disease. The priority of scientists all over the world has been to direct their time to research this subject. In this review, we highlight chemical studies and therapeutic approaches to overcome COVID-19 with seven different sections. These sections are the structure and mechanism of action of SARS-CoV-2, immunotherapy and vaccine, computer-aided drug design, repurposing therapeutics for COVID-19, synthesis of new molecular structures against COVID-19, food safety/security and functional food components, and potential natural products against COVID-19. In this work, we aimed to screen all the newly synthesized compounds, repurposing chemicals covering antiviral, anti-inflammatory, antibacterial, antiparasitic, anticancer, antipsychotic, and antihistamine compounds against COVID-19. We also highlight computer-aided approaches to develop an anti-COVID-19 molecule. We explain that some phytochemicals and dietary supplements have been identified as antiviral bioproducts, which have almost been successfully tested against COVID-19. In addition, we present immunotherapy types, targets, immunotherapy and inflammation/mutations of the virus, immune response, and vaccine issues.

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“…NM-283 (Valopicitabine) is an oral prodrug of 2′-C-methyl-cytidine, was synthesized for obtaining a molecule with higher oral bioavailability than its parent molecule, 20-C-methyl-cytidine (Pierra et al 2006 ). NM-283 is now being evaluated in phase II clinical trials for the treatment of chronic HCV infection (Tian et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

The contribution of bovines to human health against viral infections

Saied

Metwally

Mohamed

et al. 2021

Environ Sci Pollut Res

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In the last 40 years, novel viruses have evolved at a much faster pace than other pathogens. Viral diseases pose a significant threat to public health around the world. Bovines have a longstanding history of significant contributions to human nutrition, agricultural, industrial purposes, medical research, drug and vaccine development, and livelihood. The life cycle, genomic structures, viral proteins, and pathophysiology of bovine viruses studied in vitro paved the way for understanding the human counterparts. Calf model has been used for testing vaccines against RSV, papillomavirus vaccines and anti-HCV agents were principally developed after using the BPV and BVDV model, respectively. Some bovine viruses-based vaccines (BPIV-3 and bovine rotaviruses) were successfully developed, clinically tried, and commercially produced. Cows, immunized with HIV envelope glycoprotein, produced effective broadly neutralizing antibodies in their serum and colostrum against HIV. Here, we have summarized a few examples of human viral infections for which the use of bovines has contributed to the acquisition of new knowledge to improve human health against viral infections covering the convergence between some human and bovine viruses and using bovines as disease models. Additionally, the production of vaccines and drugs, bovine-based products were covered, and the precautions in dealing with bovines and bovine-based materials.

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RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic

Cited by 166 publications

References 183 publications

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

The contribution of bovines to human health against viral infections

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