Clinical Laboratory, Department of Clinical Diagnostics and Services, Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland.
Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, D-80539 Munich, Germany.
Viruses. 2022 May 17;14(5):1069. doi: 10.3390/v14051069.
As previously demonstrated by our research group, the oral multicomponent drug Xraphconn containing GS-441524 was effective at curing otherwise fatal feline infectious peritonitis (FIP) in 18 feline coronavirus (FCoV)-infected cats. The aims of the current study were to investigate, using samples from the same animals as in the previous study, (1) the effect of treatment on fecal viral RNA shedding; (2) the presence of spike gene mutations in different body compartments of these cats; and (3) viral RNA shedding, presence of spike gene mutations, and anti-FCoV antibody titers in samples of 12 companion cats cohabitating with the treated cats. Eleven of the eighteen treated FIP cats (61%) were shedding FCoV RNA in feces within the first three days after treatment initiation, but all of them tested negative by day 6. In one of these cats, fecal shedding reoccurred on day 83. Two cats initially negative in feces were transiently positive 1-4 weeks into the study. The remaining five cats never shed FCoV. Viral RNA loads in feces decreased with time comparable with those in blood and effusion. Specific spike gene mutations linked to systemic FCoV spread were consistently found in blood and effusion from treated FIP cats, but not in feces from treated or companion cats. A new mutation that led to a not yet described amino acid change was identified, indicating that further mutations may be involved in the development of FIP. Eight of the twelve companion cats shed FCoV in feces. All but one of the twelve companion cats had anti-FCoV antibodies. Oral treatment with GS-441524 effectively decreased viral RNA loads in feces, blood, and effusion in cats with FIP. Nonetheless, re-shedding can most likely occur if cats are re-exposed to FCoV by their companion cats.
如我们研究小组之前所展示的，含有 GS-441524 的口服多组分药物 Xraphconn 可有效治愈 18 只感染猫冠状病毒（FCoV）的猫的致命猫传染性腹膜炎（FIP）。本研究的目的是使用与之前研究相同的动物样本，（1）调查治疗对粪便病毒 RNA 脱落的影响；（2）这些猫不同身体部位尖峰基因突变的存在；以及（3）治疗猫同居的 12 只伴侣猫样本中的病毒 RNA 脱落、尖峰基因突变和抗 FCoV 抗体滴度。在治疗开始后的头三天内，18 只接受治疗的 FIP 猫中有 11 只（61%）粪便中 FCoV RNA 脱落，但到第 6 天它们全部检测为阴性。其中一只猫在第 83 天再次出现粪便脱落。最初粪便检测为阴性的两只猫在研究进行 1-4 周时短暂转为阳性。其余五只猫从未脱落 FCoV。粪便中病毒 RNA 载量随时间的减少与血液和渗出液中的病毒 RNA 载量相似。在接受治疗的 FIP 猫的血液和渗出液中始终发现与全身性 FCoV 传播相关的特定尖峰基因突变，但在接受治疗或伴侣猫的粪便中未发现。鉴定出一种新的突变，导致尚未描述的氨基酸改变，表明进一步的突变可能参与了 FIP 的发展。12 只伴侣猫中有 8 只粪便中脱落 FCoV。12 只伴侣猫中除 1 只外均有抗 FCoV 抗体。GS-441524 口服治疗可有效降低 FIP 猫粪便、血液和渗出液中的病毒 RNA 载量。尽管如此，如果伴侣猫使猫再次接触 FCoV，则很可能会再次脱落。
