Indinavir (Crixivan) as a Candidate for SARS-CoV-2 Antiviral Drug
A new coronavirus named SARS-CoV-2 has appeared in Wuhan, China since December 2019. It can cause severe acute respiratory symptoms (SARI) and spread quickly. As a professional drug discovery CRO company, Creative Biolabs provides one-stop protease inhibitors development services, including Indinavir. Indinavir can form a stable binding with coronavirus protease, and thus it maybe an ideal candidate for SARS-CoV-2 drug discovery.
Indinavir is a drug used as an HIV protease inhibitor. It works by binding to HIV protease active sites and inhibiting post-translational processing, leading to the formation of immature non-infectious virus particles and interruption of viral transmission. At concentrations of 25 to 100 nmol/L, Indinavir inhibited 95% of HIV replication in vitro, and in combination with other antiretroviral drugs, it has shown cumulative or synergistic antiviral effects in cell cultures in most studies. However, due to amino acid substitutions of HIV proteases, cross-resistance occurs across the entire class of protease inhibitors. In actual clinical trials, indinavir-resistant HIV clinical isolates selected during indinavir treatment have demonstrated a high degree of cross-resistance to other protease inhibitors.
In addition, there are significant differences in plasma concentrations of indinavir in patients receiving the same dose of medication. Patients with no HIV RNA detected in plasma had significantly higher drug concentrations than those with HIV RNA detected in plasma. The concentration relationship between this drug dose and antiviral effect provides good material for us to quantify the effect of heterogeneity of treatment response. Starting from this aspect, we can continue to study the pharmacological mechanism of indinavir on other viruses, especially coronavirus.
Fig.1 Molecular structure of Indinavir.
Currently, there are three general anti-virus strategies: 1) direct anti-viral effects, 2) inhibiting virus entry and replication at the cellular level by targeting virus-related processes, and 3) enhancing host immune response. In order to screen out potential protease inhibitor drugs that are effective for SARS-CoV-2, Creative Biolabs has devoted great attention to the pharmacological research and development of antiviral protease inhibitors. By analyzing the crystal structure of existing commercial drugs, we can help clients determine and evaluate whether Indinavir has potential as an effective and specific antiviral agent against this SARS-CoV-2 outbreak. In addition, we can help customers perform in vivo and in vitro tests to evaluate the actual efficacy of indinavir.
With extensive experience in antiviral drug discovery, Creative Biolabs offers high-quality validation service of Indinavir for the treatment of SARS-CoV-2. If you have any questions about our SARS-CoV-2 drug discovery services, you can contact us for more details.For Research Use Only. We do not provide services or products directly for patients.
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