A comprehensive review on the global efforts on vaccines and repurposed drugs for combating COVID-19

Kushwaha, Narva Deshwar; Mohan, Jivanka; Kushwaha, Babita; Ghazi, Terisha; Nwabuife, Joshua C.; Koorbanally, Neil A.; Chuturgoon, Anil A.

doi:10.1016/j.ejmech.2023.115719

Cited by 11 publications

(10 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the management of COVID-19 and other possible future pandemics cannot be limited to disease prevention. 1,2 Meanwhile, the development of efficient treatments directed against new viral infections requires the search for highly active, selective, and safe antiviral drugs.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The death toll of COVID-19 keeps rising despite the availability of highly efficient and broadly distributed vaccines, and the disease has already claimed nearly seven million lives globally by late 2023. Therefore, the management of COVID-19 and other possible future pandemics cannot be limited to disease prevention. , Meanwhile, the development of efficient treatments directed against new viral infections requires the search for highly active, selective, and safe antiviral drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Various known drugs are currently in the research spotlight for the possibility of being repurposed for COVID-19 treatment. − A noteworthy class of compounds that are currently being widely studied as potential SARS-CoV-2 suppressors is the derivatives of 3-hydroxypyrazine-2-carboxamide, known as compound T-1105 (Chart , compound 1a). These compounds were developed by Toyama Chemical Co., Ltd., for influenza treatment and have later been shown as potent inhibitors against nonrelated infections such as Ebola, rabies, yellow fewer, and many others. − The most notorious and researched derivative is the compound T-705 (6-fluoro-3-hydroxypyrazine-2-carboxamide, compound 1b), currently used against COVID-19 in various countries and widely known as “favipiravir”.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Designing an Efficient Biocatalyst for the Phosphoribosylation of Antiviral Pyrazine-2-carboxamide Derivatives

Zayats,

Fateev,

Abramchik

et al. 2024

ACS Catal.

View full text Add to dashboard Cite

The development of technologies for the efficient synthesis of innovative antiviral compounds remains an important challenge for modern biotechnology, especially in the context of the recent COVID-19 pandemic. One of the drugs that is currently in the research spotlight for potential anti-SARS-CoV-2 activity is the purine mimetic prodrug compound T-705, also known as favipiravir. Along with a similar compound, T-1105, the activation of T-705 is limited by the low rate of phosphoribosylation, mediated by an enzyme named hypoxanthineguanine phosphoribosyltransferase (HGPRT). Therefore, the synthesis of phosphoribosylated/ribosylated derivatives of these prodrugs is a viable direction for the discovery and development of antiviral pharmaceuticals. However, the chemical synthesis of such compounds is a complex and laborious process, whereas enzymatic cascades are not feasible because of the narrow HGPRT substrate specificity. Here, we report the successful rational design of an efficient biocatalyst for T-705/T-1105 phosphoribosylation. With two rounds of Thermus thermophilus HB27 HGPRT active site optimization, we have achieved a 325-fold increase in k cat toward the compound T-705 and a 125-fold increase toward T-1105 accompanied by a multifold decrease in K M . The practical applicability of the designed mutant was illustrated through the preparative synthesis of T-705/T-1105 nucleotide derivatives. Our engineered biocatalyst can become a basis for the technologies of enzymatic and chemoenzymatic synthesis of various T-705/T-1105 derivatives with proven antiviral activity. Moreover, our results provide insight into the molecular mechanism of T-705/T-1105 phosphoribosylation, including the experimental evidence explaining the reasons behind the low activity of HGPRT toward these compounds.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Designing an Efficient Biocatalyst for the Phosphoribosylation of Antiviral Pyrazine-2-carboxamide Derivatives

Zayats,

Fateev,

Abramchik

et al. 2024

ACS Catal.

View full text Add to dashboard Cite

show abstract

“…In addition to finding the vaccines against COVID-19, there are several ongoing searches for therapeutics acting on SARS-CoV-2 9 – 12 . Depending on the activity, the therapies against SARS-CoV-2 can be classified into two categories; one is acting on the human immune system, and the other acts on the coronavirus itself.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in silico inhibitory action studies of azo-anchored imidazo[4,5-b]indole scaffolds against the COVID-19 main protease (Mpro)

Geedkar,

Kumar,

Sharma

2024

Sci Rep

View full text Add to dashboard Cite

The present work elicits a novel approach to combating COVID-19 by synthesizing a series of azo-anchored 3,4-dihydroimidazo[4,5-b]indole derivatives. The envisaged methodology involves the l-proline-catalyzed condensation of para-amino-functionalized azo benzene, indoline-2,3-dione, and ammonium acetate precursors with pertinent aryl aldehyde derivatives under ultrasonic conditions. The structures of synthesized compounds were corroborated through FT-IR, 1H NMR, 13C NMR, and mass analysis data. Molecular docking studies assessed the inhibitory potential of these compounds against the main protease (Mpro) of SARS-CoV-2. Remarkably, in silico investigations revealed significant inhibitory action surpassing standard drugs such as Remdesivir, Paxlovid, Molnupiravir, Chloroquine, Hydroxychloroquine (HCQ), and (N3), an irreversible Michael acceptor inhibitor. Furthermore, the highly active compound was also screened for cytotoxicity activity against HEK-293 cells and exhibited minimal toxicity across a range of concentrations, affirming its favorable safety profile and potential suitability. The pharmacokinetic properties (ADME) of the synthesized compounds have also been deliberated. This study paves the way for in vitro and in vivo testing of these scaffolds in the ongoing battle against SARS-CoV-2.

show abstract

“…Clofazimine was found in at least eight independent drug-repurposing efforts [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ] and was commonly identified among the most promising compounds in those studies based on screening and antiviral assay data [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Drug-repurposing efforts are important to identify possible drugs available for clinical use when patients are not able to receive “standard-of-care” drug treatment [ 11 , 12 ]. In addition to this, ongoing studies on effective direct-acting antivirals [ 13 , 14 ] are important to understand the direct mechanism of action and the molecular basis for broad-spectrum activity.…”

Section: Introductionmentioning

confidence: 99%

The Dual-Targeted Fusion Inhibitor Clofazimine Binds to the S2 Segment of the SARS-CoV-2 Spike Protein

Freidel,

Vakhariya,

Sardarni

et al. 2024

Viruses

View full text Add to dashboard Cite

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 Spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and its derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest-quality SPR data for binding with S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results related to molecular docking and modeling of the structure–activity relationship (SAR) of a newly reported series of Clofazimine derivatives support the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure–sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronaviruses such as SARS-CoV, MERS, hCoV-229E, and hCoV-OC43.

show abstract

A comprehensive review on the global efforts on vaccines and repurposed drugs for combating COVID-19

Cited by 11 publications

References 103 publications

Designing an Efficient Biocatalyst for the Phosphoribosylation of Antiviral Pyrazine-2-carboxamide Derivatives

Designing an Efficient Biocatalyst for the Phosphoribosylation of Antiviral Pyrazine-2-carboxamide Derivatives

Synthesis and in silico inhibitory action studies of azo-anchored imidazo[4,5-b]indole scaffolds against the COVID-19 main protease (Mpro)

The Dual-Targeted Fusion Inhibitor Clofazimine Binds to the S2 Segment of the SARS-CoV-2 Spike Protein

Contact Info

Product

Resources

About