Inhibitor of Host Cell Protease for the Treatment of SARS-CoV-2

Based on our world-class equipment, facilities and highly dedicated formulation specialists, Creative Biolabs is a trusted partner and focuses on advances in research and development of inhibitors of host cell protease for the potential prophylactics and therapeutics to prevent or treat the SARS-CoV-2 infection.

Inhibitors of Host Cell Protease of SARS-CoV-2

SARS-CoV-2, belonging to the family Coronaviruses (CoVs), is a positive-sense enveloped RNA virus that causes infections in birds, mammals, and humans. Thus, a rapid drug application strategy that can be immediately applied to the patient is necessary. Currently, the only way to address this matter is to repurpose commercially available antiviral medications for the pathogen in so-called “drug-repurposing.” At present, a computational approach to screening for available commercial medicines that may function as inhibitors for the Mpro of SARS-CoV-2 has been adopted.

Ideal agents to fight SARS-CoV-2 as potential targets are protease inhibitors, components of human immunodeficiency virus (HIV) antiviral regimens. Several HIV protease inhibitors were used in prior studies of predict drugs for the SARS-CoV, including lopinavir, ritonavir, and darunavir. It is verified that they may block different aspects of the viral life cycle by inhibiting their proteases and ultimately inhibiting replication. These drugs seem effective on SARS-CoV-2 patients in the clinical application. These results demonstrate that the inhibitors of host cell protease are one of the potential drug candidates for SARS-CoV-2.

The interactions between lopinavir/ritonavir and proteases at the optimal poses.Fig.1 The interactions between lopinavir/ritonavir and proteases at the optimal poses. (Lin, 2020)

Host Cell Protease Development Service

Two antiretroviral components, lopinavir and ritonavir, are the protease enzyme used to block HIV viral replication, and it might thwart the coronavirus's protease as well. The combination of lopinavir and ritonavir among SARS-CoV patients was associated with substantial clinical benefits (fewer adverse clinical outcomes). Lopinavir/ritonavir showed the high binding ability to SARS-CoV-2 Mpro, which is similar to the previous report for SARS-CoV Mpro, indicating the potential of these drugs to function as inhibitors for coronaviruses. Creative Biolabs can provide the lopinavir/ritonavir inhibitor development services for the treatment of SARS-CoV-2 to help our customers to further study the protease inhibitors on the coronavirus action mode, efficacy, and safety.

Darunavir is an oral nonpeptidic HIV-1 protease inhibitor that is used, together with a low boosting dose of ritonavir, as part of an antiretroviral therapy regimen in treating patients with HIV-1 infection. It can selectively inhibit the cleavage of HIV gag and gag-pol polyproteins, thereby preventing viral maturation. Due to the evidence for the potential benefits of HIV-1 protease inhibitors against the SARS coronavirus (SARS-CoV), Creative Biolabs can provide darunavir inhibitor development services for the treatment of SARS-CoV-2 to help our customers to further study the protease inhibitors on the coronavirus.

With our vast experience and leading technology platforms, experts in Creative Biolabs are pleased to introduce a series of impeccable protease inhibitors services to support our customers' drug discovery and development for the treatment of SARS-CoV-2. Please feel free to contact us for more information about drug discovery for SARS-CoV-2.

Reference

  1. Lin, S.; et al. Molecular Modeling Evaluation of the Binding Abilities of Ritonavir and Lopinavir to Wuhan Pneumonia Coronavirus Proteases. bioRxiv, 2020.
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