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On January 26th Lilly and Regeneration announced that their respective meso-antibody combination therapies had performed well in Phase 3 clinical trials.
Lilly's bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) combined to reduce the risk of hospitalization and death in patients with neo-corona pneumonia (COVID-19), while regenerative antibody combination therapy REGEN-COV (REGN10933 and REGN10987) was able to prevent symptom infection by 100%.
with more than 100 million people infected with the new coronavirus (SARS-CoV-2), the two good news about meso-antibodies is tantrums for global "epidemic resistance."
, the fact that the virus is mutating has also raised concerns about the effectiveness of existing vaccines and drugs.
existing vaccines or to medritis antibodies useful in the face of virus mutations? What mutations escape key antibodies? Will virus mutations affect the efficacy of antibody drugs? Addressing these problems is of great significance in curbing the spread of the epidemic.
25, the University of Washington, Harvard Medical School's Brigham and Women's Hospital, and Howard A. Researchers at the Hughes Institute of Medicine co-published a study in Science entitled "Prospective mapping of viral mutations that escape antibodies used to treat COVID-19".
paper maps viral mutations that "escape" existing major clinical antibody drugs, covering two antibody drugs for regenerative cells and one for Lilly antibody drugs, suggesting that these drugs may not be effective against some mutations in SARS-CoV-2.
the receptor binding domain (RBD) of SARS-CoV-2 pyridrogen mediated the binding of the virus to the ACE2 receptor, and most leading anti-SARS-CoV-2 antibodies targeted the region.
A study published in September 2020 by Cell showed how all amino acid mutations in RBD affect the expression of folding proteins and their affinity for ACE2, covering 3,804 of the 3,819 possible RBD amino acid mutations.
based on this library of viral mutants, the researchers focused on how mutations in SARS-CoV-2 RBD that do not strongly destroy the combination with ACE-2 affect reGN10933, REGN10987, LY-CoV016, and REGN10933 and REGN10987 combination therapies, and use spike prosthetic slow virus particles to verify the effects of key mutations.
results show that the E406W point mutation escaped completely from the combination therapy of REGN10933 and REGN10987, and that the mutation was able to affect reGN-COV2 antibodies in a relatively specific way without seriously interfering with the function of RBD, as it only slightly reduced the moderate action of LY-CoV016 and the titularity of the spike prosthetic lyvirus particles.
evaded mutations in REGN10933, REGN10987, Ly-CoV016, and reGN10933 and REGN10987 combination therapies, can this escape map stand the test of "practice" and provide information for evolutionary analysis of viruses in the human body? To explore this problem, the researchers analyzed in-depth sequencing data from a patient with persistent infection and immunodeficiency.
the patient received a combined treatment of REN10933 and REGNO10987 on the 145th day after being diagnosed with COVID-19, and the delay in treatment time provided sufficient time for the patient's viral population to accumulate genetic diversity information.
After receiving a combination therapy of neutral antibodies, the frequency of the five amino acid mutations in viral RBD changed rapidly, showing a competitive rise and fall, a pattern previously observed in adaptive evolution within the hosts of other viruses and possibly triggered by competition between gene rides and virus lineages.
On the 145th day of infection, after screening the human-origin SARS-CoV-2 sequence as of January 11, 2021, the researchers found that a large number of RBD mutations escaped from one or more antibodies, although only three mutation sequences accounted for a percentage of the total sequence. More than 0.1%, reGN10933 escape mutant Y453F (0.3%), REGN10987 escape mutant N439K (1.7%) and LY-CoV016 escape mutant K417N (0.1%).
, Y453F is linked to outbreaks at otter farms in the Netherlands and Denmark, and K417N is found in the first-detected mutant strain B.1.351 virus lineage in South Africa.
The antibody escape mutation of SARS-CoV-2 during transmission is noteworthy, a week ago, South Africa's National Health Laboratory Service (NHLS) National Institute of Infectious Diseases (NICD), in a joint paper published by several universities in the country, suggested that the mutant strain 501Y.V2 found in South Africa could resist antibodies in plasma therapy.
in the new study, however, researchers found that the N501Y mutation did not appear to affect the effectiveness of the two meso-antibodies and Lilly's LY-CoV016.
, the study identified mutations that evade the three main anti-SARS-CoV-2 antibodies currently under study, providing an important reference for future antibody development.