Блокировка в воротах инфекции
Nov. 23rd, 2021 10:09 am![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
chuka_lisЕсть данные, что насыщенный раствор соли (3% и выше), как и апротинин, могут препятствовать проникновению коронавируса в клетки, путем блокирования работы протеазы, подрезающей фурин.
Не на 100%, но на 60-80%. Зависит от концентарции и штамма.
Что гораздо лучше чем ничего.
Активность протеаз, правда, меряли в мазках из человеческого носа, без испытаний заражением после процедуры на животных. Тк работа не для практического внедрения, а для изучения механизма, работает ли и почему.
Не знаю как на счет доступности рядовому обывателю фремента-ингибитора сериновой протеазы, но все же это -информация к размышлению, что промывания-полоскания носа (горла?) соленой водой, видимо, могут служить некоторым препятствием заражению.
It isfound the SARS-CoV-2 spike (S) glycoprotein harbors a furin cleavage; site (FCS) at the ; boundary between the S1/S2 subunits, which could be cleaved by furin and/or relevant proteases secreted from host cells. Unlike SARS-CoV, cell entry of SARS-CoV-2 needs to be pre-activated by furin and/or relevant proteases, reducing its dependence on target cell proteases forentry. The cleavage activation of&S-protein is well demonstrated to be essential forSARS-CoV-2 spike-mediated viral binding to the host ACE2 receptor, cell-cell fusion, and viral entry into human lung cells [4, 5]. It was also observed that other viruses containing a furin cleavage site, such as H5N1, displayed increased replicates and developed higher pathogenicity [6]. It was demonstrated that saline results in a dose-dependent inhibition of replication of a range of DNA and RNA viruses, including the human coronavirus 229E (HCoV-229E) [12]. Hypertonic saline nasal irrigation and gargling was also found to reduce viral upper respiratory tract infection in a clinical trial [13, 14]. Recently, hypertonic saline (1.5% NaCl) was shownto significantly inhibit replication of SARS-CoV-2 in cultured human lung and kidney epithelial cells. The major mechanism is possibly through sodium ion-mediated intracellular low energy states[15]. In this study, we observed that hypertonic saline can significantly block SARS-CoV-2-specific FCS cleavage caused by furin but not by trypsin. As S protein cleavage plays a critical role in SARS-CoV-2 activation before entry into and exiting from cells, the inhibitory effect of saline on SARS-CoV-2 replication could be at least partly due to saline blockage of furin-mediated cleavage. Aprotinin is a broad serine protease inhibitor and approved by the FDA for clinical use for reducing bleeding during complex surgery [16]. However, it showed significant antiviral effects against H1N1 influenza infections both in vitro and in vivo by blocking HA cleavage and activation and is also approved in Russia for use as a nasal aerosol for the treatment of influenza [17]. Bojkova et al recently reported that aprotinin is able to inhibitSARS-CoV-2 replication to block SARS-CoV-2-induced cytopathogenic effect (CPE) formation at therapeutically achievable concentrations [18]. Our study shows that the aprotinin effect at 3-6 μM level is remarkable in decreasing trypsin-mediated SARS-CoV-2 FCS cleavage but only moderate in inhibiting furin-based FCS cleavage.We observed that higher cleavage percentages wereachieved with both furin and trypsin for P681R FCS peptide than for wild-type one. It is consistent with that the Delta variant’s P681R allows the cleavage to occur more easily than in the wild-type SARS-CoV-2 strain, as Delta variant has a more efficient furin cleavage site [19,20]. However, the cleavage of P681R can still be inhibited by hypertonic saline or aprotinin at an appropriate concentration, even if such inhibition was relatively less in P681R FCS compared to wild-type. An interestobservation in this study is that the combination of hypertonic saline and aprotinin achieved nearly complete inhibition of FCS cleavage in both wild-type and P681R mutantwith use of nasal swab samples, although hypertonic saline or aprotinin alone only has moderate and mild inhibitory effect on both wild-type and P618R mutant, respectively.
SARS-CoV-2 enters into the human body mainly through the nasal epithelial cells. Cell entry of SARS-CoV-2 needs to be pre-activated by S1/S2 boundary furin motif cleavage by furin and/or relevant proteases. It is important to locally block SARS-CoV-2 S1/S2 site cleavage caused by furin and other relevant protease activity in the nasal cavity. We tested hypertonic saline and aprotinin-based blockage of SARS-CoV-2 specific furin site cleavage by furin, trypsin and nasal swab samples containing nasal proteases. Our results show that saline and aprotinin block SARS-Cov-2 specific furin site cleavage and that a saline and aprotinin combination could significantly reduce SARS-Cov-2 wild-type and P681R mutant furin site cleavage by inhibition of nasal protease activity.
Не на 100%, но на 60-80%. Зависит от концентарции и штамма.
Что гораздо лучше чем ничего.
Активность протеаз, правда, меряли в мазках из человеческого носа, без испытаний заражением после процедуры на животных. Тк работа не для практического внедрения, а для изучения механизма, работает ли и почему.
Не знаю как на счет доступности рядовому обывателю фремента-ингибитора сериновой протеазы, но все же это -информация к размышлению, что промывания-полоскания носа (горла?) соленой водой, видимо, могут служить некоторым препятствием заражению.
It isfound the SARS-CoV-2 spike (S) glycoprotein harbors a furin cleavage; site (FCS) at the ; boundary between the S1/S2 subunits, which could be cleaved by furin and/or relevant proteases secreted from host cells. Unlike SARS-CoV, cell entry of SARS-CoV-2 needs to be pre-activated by furin and/or relevant proteases, reducing its dependence on target cell proteases forentry. The cleavage activation of&S-protein is well demonstrated to be essential forSARS-CoV-2 spike-mediated viral binding to the host ACE2 receptor, cell-cell fusion, and viral entry into human lung cells [4, 5]. It was also observed that other viruses containing a furin cleavage site, such as H5N1, displayed increased replicates and developed higher pathogenicity [6]. It was demonstrated that saline results in a dose-dependent inhibition of replication of a range of DNA and RNA viruses, including the human coronavirus 229E (HCoV-229E) [12]. Hypertonic saline nasal irrigation and gargling was also found to reduce viral upper respiratory tract infection in a clinical trial [13, 14]. Recently, hypertonic saline (1.5% NaCl) was shownto significantly inhibit replication of SARS-CoV-2 in cultured human lung and kidney epithelial cells. The major mechanism is possibly through sodium ion-mediated intracellular low energy states[15]. In this study, we observed that hypertonic saline can significantly block SARS-CoV-2-specific FCS cleavage caused by furin but not by trypsin. As S protein cleavage plays a critical role in SARS-CoV-2 activation before entry into and exiting from cells, the inhibitory effect of saline on SARS-CoV-2 replication could be at least partly due to saline blockage of furin-mediated cleavage. Aprotinin is a broad serine protease inhibitor and approved by the FDA for clinical use for reducing bleeding during complex surgery [16]. However, it showed significant antiviral effects against H1N1 influenza infections both in vitro and in vivo by blocking HA cleavage and activation and is also approved in Russia for use as a nasal aerosol for the treatment of influenza [17]. Bojkova et al recently reported that aprotinin is able to inhibitSARS-CoV-2 replication to block SARS-CoV-2-induced cytopathogenic effect (CPE) formation at therapeutically achievable concentrations [18]. Our study shows that the aprotinin effect at 3-6 μM level is remarkable in decreasing trypsin-mediated SARS-CoV-2 FCS cleavage but only moderate in inhibiting furin-based FCS cleavage.We observed that higher cleavage percentages wereachieved with both furin and trypsin for P681R FCS peptide than for wild-type one. It is consistent with that the Delta variant’s P681R allows the cleavage to occur more easily than in the wild-type SARS-CoV-2 strain, as Delta variant has a more efficient furin cleavage site [19,20]. However, the cleavage of P681R can still be inhibited by hypertonic saline or aprotinin at an appropriate concentration, even if such inhibition was relatively less in P681R FCS compared to wild-type. An interestobservation in this study is that the combination of hypertonic saline and aprotinin achieved nearly complete inhibition of FCS cleavage in both wild-type and P681R mutantwith use of nasal swab samples, although hypertonic saline or aprotinin alone only has moderate and mild inhibitory effect on both wild-type and P618R mutant, respectively.
SARS-CoV-2 enters into the human body mainly through the nasal epithelial cells. Cell entry of SARS-CoV-2 needs to be pre-activated by S1/S2 boundary furin motif cleavage by furin and/or relevant proteases. It is important to locally block SARS-CoV-2 S1/S2 site cleavage caused by furin and other relevant protease activity in the nasal cavity. We tested hypertonic saline and aprotinin-based blockage of SARS-CoV-2 specific furin site cleavage by furin, trypsin and nasal swab samples containing nasal proteases. Our results show that saline and aprotinin block SARS-Cov-2 specific furin site cleavage and that a saline and aprotinin combination could significantly reduce SARS-Cov-2 wild-type and P681R mutant furin site cleavage by inhibition of nasal protease activity.
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Date: 2021-11-23 07:19 pm (UTC)То-то я последний месяц на соленую треску налегаю.
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Date: 2021-11-23 10:34 pm (UTC)no subject
Date: 2021-11-23 10:44 pm (UTC)Да, он у меня сообразительный.
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Date: 2021-11-25 12:22 am (UTC)no subject
Date: 2021-11-25 04:48 pm (UTC)