Publications by authors named "B Sprenger"
Nirmatrelvir was the first protease inhibitor specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir.
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- The two approved antivirals for SARS-CoV-2, nirmatrelvir (with ritonavir) and ensitrelvir, are effective but may face challenges from resistance mutations.
- Studying these mutations is crucial for treatment strategies, though generating resistant viruses is controversial due to safety concerns.
- Using a safe virus system, researchers identified specific resistance mutations against ensitrelvir, while nirmatrelvir maintained effectiveness, indicating distinct resistance profiles that could influence treatment choices.
Article Synopsis
- MERS-CoV, a zoonotic virus first reported in Saudi Arabia in 2012, poses a serious threat due to its high mortality rate of up to 35% and potential to mutate, necessitating the development of antiviral treatments.
- Recent research has focused on protease inhibitors developed for SARS-CoV-2 to assess their effectiveness against MERS-CoV, revealing that the drug nirmatrelvir notably inhibits several relevant proteases.
- The study also simulated nirmatrelvir's clinical use against MERS-CoV, analyzing the development of resistance through various MERS-CoV mutant strains and specific mutations in their catalytic sites.
Article Synopsis
- Nirmatrelvir, the first protease inhibitor designed for SARS-CoV-2, faces potential resistance as the virus continues to evolve.
- This study aimed to identify mutations that enable resistance by exposing a modified virus to increasing levels of nirmatrelvir, leading to the selection of various resistant mutants.
- The research not only characterizes these resistance mutations but also explores their implications for future drug development and treatment strategies against SARS-CoV-2.
Fusion protein technologies improve the expression and purification of recombinant proteins, but the removal of the tags involved requires specific proteases. The circularly permuted caspase-2 (cpCasp2) with its specific cleavage site, efficiently generates the untagged protein. While cleavage with cpCasp2 is possible before all 20 proteinogenic amino acids, cleavage before valine, leucine, isoleucine, aspartate and glutamate suffers from slow, and before proline extremely slow, turnover.
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