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Jun. 27th, 2021 12:03 am![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
chuka_lisПрепринт, в котором показано, что витамин В12 может подавлять размножение коронавируса.
Авторы провели сначала компьютерный анализ "теоретически подходящих" вариантов из уже имеющихся веществ "банка лекарств" (молекулярное моделирование), а затем проверили самые подходящие варианты и на культуре клеток. Кроме аналогов ремдесивира (оба вещества - нуклеотидные аналоги, пробовавшиеся для лечения гепатита С, тоже "про-лекарства", как и он; одно из которых, правда, токсичное) в сеть попался и цианкобаламин.
Да, как контроль у них там был ремдесивир (см. рис 5)- и он в самом деле не давал вирусу размножаться в культуре, а метилкобаламин в концентрации 500 мкг был весьма эффективен (в зависимости от культуры клеток, изолята вируса он и другие "изо"формы витамина- ингибировали вирус на 50-97%).
We then determined the half maximal inhibitory concentration (IC50) values in cell culture models( in VeroE6 and Caco-2 cells) of SARS-CoV-2 infection and assessed cytotoxicity. Lastly, we demonstrated efficacy against several variants including SARS-CoV-2 Strain England 2 (England 02/2020/407073), B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). Our data reveal that BMS-986094 and different forms of vitamin B12 are effective at inhibiting replication of all these variants of SARS-CoV-2. Consistent with earlier data, BMS and all forms of vitamin B12 suppressed the replication of this panel of SARS-CoV-2 isolates to similar degrees While BMS-986094 can cause secondary effects in humans as established by phase II trials, these findings suggest that vitamin B12 deserves consideration as a SARS-CoV-2 antiviral, particularly given its extended use and lack of toxicity in humans, and its availability and affordability.
Our data demonstrated that several forms of vitamin B12 inhibit SARS-CoV-2 replication in vitroin two different cell lines(Figures 3-5). In humans, injections of up to 10mg have not shown side effects. The healthy range of vitamin B12 in blood is 118-701 pM. Vitamin B12 deficiency is treated with injections of 1mghydroxocobalamin44, with 1mg/mL hydroxocobalaminbeing 742.2μM. Higher doses of hydroxocobalamin are however tolerated. Upon cyanide poisoning, adults can receive up to 5g of hydroxocobalamin as an antidote intravenously, which would be well within the range of our calculated IC50of 403μM.Moreover, previous studies on imaging show biodistribution of an intravenous In-111 labeled 5-deoxyadenosylcobalamin (AC) analog ([111In]AC) in nasal cavity and salivary glands45. There is also previous evidence of vitamin B12 having potential antiviral effects. An in silico screening by Narayan an and Nair46showed their second best docking score between methylcobalamin and nsp12 (the gene that encodes for RdRP). Vitamin B12 has been shown to improve outcome in hepatitis C virus (HCV) infection. HCV isa single-strandedRNA virusthathasan internal ribosomal entry site (IRES) which interacts with cellular ribosomal subunits, and vitamin B12has been reported towork by inhibitingHCVIRES-dependent translation.47Interestingly, BMS was originally designed against HCV.48 BMS warrant sfurther investigation, while vitamin B12 is readily available from multiple sources, it is affordable, can be self-administered by patients,is available worldwide, and displays low-to-no toxicity at high doses.
Авторы провели сначала компьютерный анализ "теоретически подходящих" вариантов из уже имеющихся веществ "банка лекарств" (молекулярное моделирование), а затем проверили самые подходящие варианты и на культуре клеток. Кроме аналогов ремдесивира (оба вещества - нуклеотидные аналоги, пробовавшиеся для лечения гепатита С, тоже "про-лекарства", как и он; одно из которых, правда, токсичное) в сеть попался и цианкобаламин.
Да, как контроль у них там был ремдесивир (см. рис 5)- и он в самом деле не давал вирусу размножаться в культуре, а метилкобаламин в концентрации 500 мкг был весьма эффективен (в зависимости от культуры клеток, изолята вируса он и другие "изо"формы витамина- ингибировали вирус на 50-97%).
We then determined the half maximal inhibitory concentration (IC50) values in cell culture models( in VeroE6 and Caco-2 cells) of SARS-CoV-2 infection and assessed cytotoxicity. Lastly, we demonstrated efficacy against several variants including SARS-CoV-2 Strain England 2 (England 02/2020/407073), B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). Our data reveal that BMS-986094 and different forms of vitamin B12 are effective at inhibiting replication of all these variants of SARS-CoV-2. Consistent with earlier data, BMS and all forms of vitamin B12 suppressed the replication of this panel of SARS-CoV-2 isolates to similar degrees While BMS-986094 can cause secondary effects in humans as established by phase II trials, these findings suggest that vitamin B12 deserves consideration as a SARS-CoV-2 antiviral, particularly given its extended use and lack of toxicity in humans, and its availability and affordability.
Our data demonstrated that several forms of vitamin B12 inhibit SARS-CoV-2 replication in vitroin two different cell lines(Figures 3-5). In humans, injections of up to 10mg have not shown side effects. The healthy range of vitamin B12 in blood is 118-701 pM. Vitamin B12 deficiency is treated with injections of 1mghydroxocobalamin44, with 1mg/mL hydroxocobalaminbeing 742.2μM. Higher doses of hydroxocobalamin are however tolerated. Upon cyanide poisoning, adults can receive up to 5g of hydroxocobalamin as an antidote intravenously, which would be well within the range of our calculated IC50of 403μM.Moreover, previous studies on imaging show biodistribution of an intravenous In-111 labeled 5-deoxyadenosylcobalamin (AC) analog ([111In]AC) in nasal cavity and salivary glands45. There is also previous evidence of vitamin B12 having potential antiviral effects. An in silico screening by Narayan an and Nair46showed their second best docking score between methylcobalamin and nsp12 (the gene that encodes for RdRP). Vitamin B12 has been shown to improve outcome in hepatitis C virus (HCV) infection. HCV isa single-strandedRNA virusthathasan internal ribosomal entry site (IRES) which interacts with cellular ribosomal subunits, and vitamin B12has been reported towork by inhibitingHCVIRES-dependent translation.47Interestingly, BMS was originally designed against HCV.48 BMS warrant sfurther investigation, while vitamin B12 is readily available from multiple sources, it is affordable, can be self-administered by patients,is available worldwide, and displays low-to-no toxicity at high doses.
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