Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.
Unilever Research & Development Centre, Unilever Industries Private Limited, 64, Whitefield Main Road, Bangalore, 560066, India.
BMC Microbiol. 2024 Oct 17;24(1):413. doi: 10.1186/s12866-024-03565-1.
Non-enveloped viruses, which lack a lipid envelope, display higher resistance to disinfectants, soaps and sanitizers compared to enveloped viruses. The capsids of these viruses are highly stable and symmetric protein shells that resist inactivation by commonly employed virucidal agents. This group of viruses include highly transmissible human pathogens such as Rotavirus, Poliovirus, Foot and Mouth Disease Virus, Norovirus and Adenovirus; thus, devising appropriate strategies for chemical disinfection is essential.
In this study, we tested a mild, hypoallergenic combination of a denaturant, alcohol, and organic acid (3.2% citric acid, 1% urea and 70% ethanol, pH4) on two representative non-enveloped viruses - Human Adenovirus 5 (HAdV5) and Feline Calicivirus (FCV)- and evaluated the pathways of capsid neutralization using biophysical methods. The conformational shifts in the capsid upon chemical treatment were studied using Differential Scanning Calorimetry (DSC), while the morphological alterations were visualized concurrently using Transmission Electron Microscopy (TEM). We found that while treatment of purified HAdV5 particles with a formulation resulted in thermal instability and, large scale aggregation; similar treatment of FCV particles resulted in complete collapse of the capsids. Further, while individual components of the formulation caused significant damage to the capsids, a synergistic action of the whole formulation was evident against both non-enveloped viruses tested.
The distinct effects of the chemical treatment on the morphology of HAdV5 and FCV suggests that non-enveloped viruses with icosahedral geometry can follow different morphological pathways to inactivation. Synergistic effect of whole formulation is more effective compared to individual components. Molecular level understanding of inactivation pathways may result in the design and development of effective mass-market formulations for rapid neutralization of non-enveloped viruses.
无包膜病毒缺乏脂质包膜，与包膜病毒相比，它们对消毒剂、肥皂和消毒剂具有更高的抵抗力。这些病毒的衣壳是高度稳定和对称的蛋白质外壳，能够抵抗常用的杀病毒剂的失活。这组病毒包括高度传染性的人类病原体，如轮状病毒、脊髓灰质炎病毒、口蹄疫病毒、诺如病毒和腺病毒；因此，设计适当的化学消毒策略至关重要。
在这项研究中，我们测试了一种温和的、低变应原的变性剂、酒精和有机酸（3.2%柠檬酸、1%尿素和 70%乙醇，pH4）混合物对两种代表性的无包膜病毒——人腺病毒 5（HAdV5）和猫杯状病毒（FCV）的影响，并使用生物物理方法评估了衣壳中和的途径。使用差示扫描量热法（DSC）研究了衣壳在化学处理后的构象变化，同时使用透射电子显微镜（TEM）同时观察形态变化。我们发现，虽然用制剂处理纯化的 HAdV5 颗粒会导致热不稳定性和大规模聚集；但类似地处理 FCV 颗粒会导致衣壳完全崩溃。此外，虽然制剂的各个成分对衣壳造成了显著的损伤，但整个制剂的协同作用对两种测试的无包膜病毒都很明显。
化学处理对 HAdV5 和 FCV 形态的不同影响表明，具有二十面体几何形状的无包膜病毒可以遵循不同的形态途径进行失活。整个制剂的协同作用比单个成分更有效。对失活途径的分子水平理解可能导致设计和开发有效的大众市场制剂，用于快速中和无包膜病毒。
