Advances in research on 3C-like protease (3CL<sup>pro</sup>) inhibitors against SARS-CoV-2 since 2020

Chen, Roufen; Gao, Yali; Liu, Han; Li, He; Chen, Wen-Fa; Ma, Junjie

doi:10.1039/d2md00344a

Cited by 24 publications

(14 citation statements)

References 81 publications

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“…The 3CL pro , also known as Mpro, is an enzyme that plays a crucial role in the replication of several coronaviruses, including SARS-CoV-2 and FIPV. This enzyme is essential for viral replication because it cleaves the virus-produced polyproteins into functional mature proteins that are required for viral replication and assembly. , The SARS-CoV-2 3CL pro amino acid sequence was highly similar to that of FIPV (44% sequence identity) and had similar properties (97% match) (Figure a). FIPV infection of CRFK cells demonstrated that PQQ inhibits viral replication.…”

Section: Resultsmentioning

confidence: 99%

Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection

Mohamad Ishak,

Numaguchi,

Ikemoto

2023

ACS Omega

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The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus disease (COVID-19) is ongoing. Therefore, effective prevention of virus infection is required. Pyrroloquinoline quinone (PQQ), a natural compound found in various foods and human breast milk, plays a role in various physiological processes and is associated with health benefits. In this study, we aimed to determine the effects of PQQ on preventing coronavirus infections using a proxy Feline Infectious Peritonitis Virus (FIPV; belongs to the coronavirus family). In plaque reduction assays, we showed that pre-and post-PQQ-treated viruses were less infectious. IC 50 was 87.9 and 5.1 μM for pre-and post-PQQ-treated viral infections, respectively. These results suggest that PQQ decreased the virion stability and viral replication. RT-qPCR confirmed these results. TEM findings showed that PQQ damaged viral capsids and aggregated viral particles, leading to inhibited virus attachment and entry into the host cells. PQQ was optimized by the addition of ascorbic acid and glutamic acid, which increased the number of redox cycles of PQQ and increased reactive oxygen species production by 14 times. In vitro, PQQ inhibited 3 CL pro /M pro enzymes (an enzyme critical for viral replication) activity of SARS-CoV-2. Our results demonstrate the antiviral effect of PQQ on coronavirus, mainly by disrupting virion stability and loss of infectivity (occurring outside the host cell), due to increased redox activity. Furthermore, PQQ may hinder viral replication (inside the host cell) by 3 CL pro /M pro enzyme inhibition. In summary, this study demonstrates the antiviral effect of PQQ and its potential application in coronavirus diseases.

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Section: Resultsmentioning

confidence: 99%

Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection

Mohamad Ishak,

Numaguchi,

Ikemoto

2023

ACS Omega

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“…2) for the treatment in of COVID-19. This again signifies the importance of the fluorine atom (Assmus et al 2022;Ghosh et al 2022;Li et al 2022;Veeramani et al 2023;Chen et al 2023;Gahbauer et al 2023;Kneller et al 2022;Sasaki et al 2023).…”

Section: Fluorinated Drugs Recommended During the Covid-19 Pandemicmentioning

confidence: 90%

Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

et al. 2023

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During the last twenty years, organic fluorination chemistry established itself as an important tool to get a biologically active compound. This belief can be supported by the fact that every year, we are getting fluorinated drugs in the market in extremely significant numbers. Last year, also ten fluorinated drugs have been approved by FDA and during the COVID-19 pandemic, fluorinated drugs played a very crucial role to control the disease and saved many lives. In this review, we surveyed all ten fluorinated drugs approved by FDA in 2021 and all fluorinated drugs which were directly-indirectly used during the COVID-19 period, and emphasis has been given particularly to their synthesis, medicinal chemistry, and development process. Out of ten approved drugs, one drug pylarify, a radioactive diagnostic agent for cancer was approved for use in positron emission tomography imaging. Also, very briefly outlined the significance of fluorinated drugs through their physical, and chemical properties and their effect on drug development.

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“…The team of Yang Haitao and Rao Zihe and that of Jiang Hualiang used computer-aided drug design to determine a potential inhibitor 13 (N3) (Figure 1(a)) for the main protease M pro of SARS-CoV-2, 41 which contains a Michael acceptor as a warhead and can effectively fight against a variety of coronaviruses, including SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). 42 indicating that these parts may not be the key to inhibiting the activity. The structure of these parts can be optimized to improve the efficacy and pharmacokinetic characteristics.…”

Section: Michael Acceptormentioning

confidence: 99%

“…The team of Yang Haitao and Rao Zihe and that of Jiang Hualiang used computer-aided drug design to determine a potential inhibitor 13 (N3) (Figure 1(a)) for the main protease M pro of SARS-CoV-2, 41 which contains a Michael acceptor as a warhead and can effectively fight against a variety of coronaviruses, including SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). 42 Compound 13 has antiviral effects in SARS-CoV-2-infected Vero cells (EC 50 = 16.77 μM). The crystal structure of the complex of SARS-CoV-2 M pro and inhibitor 13 was analyzed (PDB 6LU7).…”

Section: Targeted Inhibitors Of Sars-cov-2 Main Proteasementioning

confidence: 99%

“…The N -methylpiperazine group is located outside the catalytic pocket, and the absence of 23 is observed in the S1′ and S4 pockets, indicating that structural optimization can be carried out in these places to further improve the inhibitory activity of M pro while reducing the inhibitory activity of tyrosine kinase and reducing the related side effects. 42…”

Section: Targeted Inhibitors Of Sars-cov-2 Main Proteasementioning

confidence: 99%

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M^pro-targeted anti-SARS-CoV-2 inhibitor-based drugs

She

Yao

Wang

et al. 2023

Journal of Chemical Research

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The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global health emergency. The main protease is an important drug target in coronaviruses. It plays an important role in the processing of viral RNA-translated polyproteins and is highly conserved in the amino acid sequence and three-dimensional structure, making it a good drug target for which several small molecule inhibitors are available. This paper describes the various anti-severe acute respiratory syndrome coronavirus 2 inhibitor drugs targeting Mpro discovered since the severe acute respiratory syndrome coronavirus 2 outbreak at the end of 2019, with all these compounds inhibiting severe acute respiratory syndrome coronavirus 2 Mpro activity in vitro. This provides a reference for the development of severe acute respiratory syndrome coronavirus 2 Mpro-targeted inhibitors and the design of therapeutic approaches to address newly emerged severe acute respiratory syndrome coronavirus 2 mutant strains with immune evasion capabilities.

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Advances in research on 3C-like protease (3CL^pro) inhibitors against SARS-CoV-2 since 2020

Abstract: COVID-19 caused by SARS-CoV-2 in late 2019 is still threatening global human health. Although some vaccines and drugs are available in market, controlling the spread of the SARS-CoV-2 virus remains...

Cited by 24 publications

References 81 publications

Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection

Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection

Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

M^pro-targeted anti-SARS-CoV-2 inhibitor-based drugs

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Advances in research on 3C-like protease (3CLpro) inhibitors against SARS-CoV-2 since 2020

Abstract: COVID-19 caused by SARS-CoV-2 in late 2019 is still threatening global human health. Although some vaccines and drugs are available in market, controlling the spread of the SARS-CoV-2 virus remains...

Cited by 24 publications

References 81 publications

Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection

Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection

Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

Mpro-targeted anti-SARS-CoV-2 inhibitor-based drugs

Contact Info

Product

Resources

About

Advances in research on 3C-like protease (3CL^pro) inhibitors against SARS-CoV-2 since 2020

M^pro-targeted anti-SARS-CoV-2 inhibitor-based drugs