Structural stability of SARS-CoV-2 virus like particles degrades with temperature

Abstract

SARS-CoV-2 is a novel coronavirus which has caused the COVID-19 pandemic. Other known coronaviruses show a strong pattern of seasonality, with the infection cases in humans being more prominent in winter. Although several plausible origins of such seasonal variability have been proposed, its mechanism is unclear. SARS-CoV-2 is transmitted via airborne droplets ejected from the upper respiratory tract of the infected individuals. It has been reported that SARS-CoV-2 can remain infectious for hours on surfaces. As such, the stability of viral particles both in liquid droplets as well as dried on surfaces is essential for infectivity. Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. We demonstrate that even a mild temperature increase, commensurate with what is common for summer warming, leads to dramatic disruption of viral structural stability, especially when the heat is applied in the dry state. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter.

Keywords: SARS-CoV-2; Stability; Temperature; Virus-like particle.

Fig. 1

Sars-CoV-2 VLP stability as a function of environmental conditions. (A) VLPs are stable for hours on glass surfaces at room temperature under dry conditions. (B) VLPs imaged at 34 °C under dry conditions show high background noise and negligibly few features consistent with (A). MT washout sites can only be identified via high contrast enhancement (Fig. S1) and spatial peaks indicative of VLPs are rare and fragile (Fig. 2). (C) VLPs incubated at 34 °C in solution and imaged at room temperature are more consistent with (A) but also reveal widespread VLP disruption.

Fig. 2

Sars-CoV-2 VLP disintegrates readily when AFM scanned at 34C. Surface features consistent with individual VLPs are extremely rare. Even when such features are found in large area surveys (left), they cannot be scanned a second time, e.g. to obtain a zoomed in view (right). Zoom are is highlight on the left via a rectangle outline. The particles become flatter and show lateral spread consistent with mechanical VLP destruction [10].

Fig. 3

Temperature dependence of Z-height distributions of surface features. (A) Surface features have a strongly peaked height distribution consistent with air dried VLPs at 22 °C. The median height of the particles is 43.4–51.4 nm (n = 37). (B) Features observed at 34 °C have median height 14.6–22.3 nm (n = 31). CI estimated via bootstrap with 1e3 resamplings.