Lopinavir/Ritonavir for the Treatment of SARS-CoV-2

Based on our innovative research techniques and unparalleled experience and expertise, Creative Biolabs can provide investigational lopinavir/ritonavir inhibitor development services to support your coronavirus research and drug discovery process.

Lopinavir/Ritonavir Protease Inhibitor

Lopinavir is a novel highly potent and selective protease inhibitor for the HIV-1 protease, which is an essential enzyme for the production of mature, infective viruses. It acts by arresting the maturation of HIV-1, thereby blocking its infectivity. Coadministration with structurally related low-dose ritonavir as a pharmacokinetic enhancer significantly has the antiviral action and can improve the pharmacokinetic properties and hence the activity of lopinavir against protease.

Lopinavir and/or ritonavir have anti-coronavirus activity in vitro, and several reports have indicated that these HIV-1 protease inhibitors have the potential for studying the early treatment of severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) coronaviruses. In particular, the combination of lopinavir and ritonavir exhibits encouraging signs of being a substantial clinical benefit and fewer adverse clinical outcomes in a historical clinical trial among the SARS virus patients. Moreover, lopinavir is believed to act on the intracellular processes of coronavirus replication and demonstrated reduced mortality in preclinical data available and limited clinical benefit.

Fig.1 Docking model of ritonavir to 2019-nCoV M^pro. (Liu, 2020)

Lopinavir/Ritonavir for SARS-CoV-2 Treatment

Based on the predict drug-target interactions (DTIs) of SARS-CoV-2 and homology modeling, ritonavir has been shown to inhibit the CoV proteinase in line with the inhibitory potency of lopinavir. The sequence and structural conservation of lopinavir/ritonavir bind site between SARS-CoV and SARS-CoV-2 have been evaluated 96% identical. Virtual docking of lopinavir/ritonavir to SARS-CoV-2 M^pro also showed a high binding ability to the pocket site, similar to the previous report for the spatial structure of SARS-CoV M^pro, leading to the estimate of their inhibitor effects on these proteases preliminarily. Although there is no real-world evidence about whether these drugs will act as predicted against SARS-CoV-2 yet, some case studies have been identified.

Lopinavir/Ritonavir Development Services

Creative Biolabs can provide a number of lopinavir/ritonavir protease inhibitor services to help our customers for further researches of the treatment of SARS-CoV-2, including but not limited to:

• The catalytic mechanism, the structure, and dynamic behaviors study and antiviral activity assays
• In vitro/in vivo pharmacodynamics studies to assess pharmacodynamics (PD) for therapeutic compounds
• In vitro ADME to evaluate drug absorption, distribution, metabolism, excretion, and toxicology
• In vivo PK studies for all aspects of in vivo pharmacokinetic support
• Prophylactic in vivo efficacy studies to determine if drug regimens could affect virus replication and/or disease progression
• Pharmacology studies and builds various animal models to describe the effect in response to drug dose
• Toxicity study and safety evaluation for preclinical and dosage and administration

With our well-trained, knowledgeable medicinal chemists and over years of experience in drug discovery, Creative Biolabs provides high-quality, accurate drug candidates for our customers all over the world. Please feel free to contact us for more information about drug discovery for SARS-CoV-2.

Reference

1. Liu, X.; Wang, X. J. Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines. bioRxiv, 2020.

For Research Use Only. We do not provide direct services or products for patients.