Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters.
Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters.
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DOI：
10.3390/v15112161
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发表时间：
2023-10-27
期刊：
影响因子：
--
通讯作者：
Owen A
中科院分区：
文献类型：
--
作者：
Gallardo-Toledo E;Neary M;Sharp J;Herriott J;Kijak E;Bramwell C;Curley P;Arshad U;Pertinez H;Rajoli RKR;Valentijn A;Cox H;Tatham L;Kipar A;Stewart JP;Owen A
吡布伦塔韦(Pibrentasvir，PIB)已被证明可以阻断SARS-CoV-2聚合酶的外切酶活性，保护法韦拉韦(Fvp)和雷米普韦(Rdv)不被掺入后切除，并在体外诱导抗病毒协同作用。本研究采用叙利亚金黄地鼠接触传播模型，观察了PIB、FvP、RDV、FvP加PIB或RDV加PIB，一天两次滴鼻给药的预防效果。与生理盐水对照组相比，FVP(第7天)、RDV(第3、5、7天)和RDV+PIB(第3、5天)治疗组咽拭子中病毒RNA水平显著降低。同样，PIB和RDV治疗后的鼻甲和第7天的PIB、FvP和FvP+PIB治疗后的肺也有明显的发现。RDV和RDV+PIB治疗后的肺病毒RNA水平每组只有两只动物检测到，但总体差异没有统计学意义。肺的原位检查证实所有动物都感染了SARS-CoV-2，但RDV和RDV+PIB治疗组各有一只，在所有病毒检测方法中均为阴性。总体而言，在大多数接受RDV治疗的动物中观察到了预防传播，而其他制剂则减少了接触传播后的病毒载量。未观察到FVP或RDV与PIB联合应用的益处。
Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed.
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影响因子：
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DOI：
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发表时间：
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影响因子：
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