Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2

Zhao, Hanjun; To, Kelvin Kai-Wang; Lam, Hoiyan; Zhou, Xinxin; Chan, Jasper Fuk‐Woo; Zheng, Peng; Lee, Andrew Chak-Yiu; Cai, Jian‐Piao; Chan, Wan-Mui; Ip, Jonathan Daniel; Chan, Chris; Yeung, Man Lung; Zhang, Anna Jinxia; Chu, Allen Wing Ho; Jiang, Shibo; Yuen, Kwok‐Yung

doi:10.1038/s41467-021-21825-w

Cited by 46 publications

(51 citation statements)

References 48 publications

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“…The 8P9R can inhibit the two entry pathways of SARS-CoV-2 in cells including endocytic pathway and TMPRSS2-mediated surface pathway by aggregating viral particles. In addition, 8P9R, or the combination of repurposed drugs, arbidol, chloroquine and camostat could significantly suppress SARS-CoV-2 replication in hamsters and SARS-CoV in mice 185 .…”

Section: Small-molecule Sars-cov-2 Inhibitors Targeting Host Proteinsmentioning

confidence: 98%

Recent advances in developing small-molecule inhibitors against SARS-CoV-2

Xiang

Wang

et al. 2022

Acta Pharmaceutica Sinica B

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The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

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Section: Small-molecule Sars-cov-2 Inhibitors Targeting Host Proteinsmentioning

confidence: 98%

Recent advances in developing small-molecule inhibitors against SARS-CoV-2

Xiang

Wang

et al. 2022

Acta Pharmaceutica Sinica B

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“…HD5 blocked ACE2 receptors on host cells (214). The cross-linking peptide 8P9R showed potent antiviral activity against SARS-CoV-2 by cross-linking viruses to reduce viral entry on cell surface, and by interfering endosomal acidification to block viral entry through endocytic pathway (215).…”

Section: Peptide Inhibiting Viral Entry and Replicationmentioning

confidence: 99%

Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update

et al. 2021

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.

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“…A study by Ou et al found that the Cathepsin L inhibitor, SID 26681509, independently decreased SARS-CoV-2 S pseudovirion entry by about 76% at 2 μM [ 155 ]. The P9 derivates, P9R and 8P9R, have also shown significant activity against SARS-CoV and SARS-CoV-2 ranging in the low micro- to nanomolar range [ 156 , 157 ]. More importantly, 8P9R demonstrated antiviral activity by decreasing the SARS-CoV-2 viral load in vivo in mice and hamsters [ 157 ].…”

Section: Host Proteases and Endosome Acidification Inhibitorsmentioning

confidence: 99%

Keep out! SARS-CoV-2 entry inhibitors: their role and utility as COVID-19 therapeutics

Chitsike

Duerksen-Hughes

2021

Virol J

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The COVID-19 pandemic has put healthcare infrastructures and our social and economic lives under unprecedented strain. Effective solutions are needed to end the pandemic while significantly lessening its further impact on mortality and social and economic life. Effective and widely-available vaccines have appropriately long been seen as the best way to end the pandemic. Indeed, the current availability of several effective vaccines are already making a significant progress towards achieving that goal. Nevertheless, concerns have risen due to new SARS-CoV-2 variants that harbor mutations against which current vaccines are less effective. Furthermore, some individuals are unwilling or unable to take the vaccine. As health officials across the globe scramble to vaccinate their populations to reach herd immunity, the challenges noted above indicate that COVID-19 therapeutics are still needed to work alongside the vaccines. Here we describe the impact that neutralizing antibodies have had on those with early or mild COVID-19, and what their approval for early management of COVID-19 means for other viral entry inhibitors that have a similar mechanism of action. Importantly, we also highlight studies that show that therapeutic strategies involving various viral entry inhibitors such as multivalent antibodies, recombinant ACE2 and miniproteins can be effective not only for pre-exposure prophylaxis, but also in protecting against SARS-CoV-2 antigenic drift and future zoonotic sarbecoviruses.

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Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2

Cited by 46 publications

References 48 publications

Recent advances in developing small-molecule inhibitors against SARS-CoV-2

Recent advances in developing small-molecule inhibitors against SARS-CoV-2

Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update

Keep out! SARS-CoV-2 entry inhibitors: their role and utility as COVID-19 therapeutics

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