In a recent paper available on the bioRxiv* preprint server, US researchers show that individual particles of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) undergo structural destabilization at relatively mild but elevated temperatures – strengthening the case for coronavirus disease (COVID-19) resurgence in the winter.
A common transmission route for SARS-CoV-2, the causative agent of COVID-19 disease, is through aerosols created during sharp exhalation events, such as coughing or sneezing. Furthermore, it is known that viral particles frequently spread after their deposition on different surfaces.
Transmission electron micrograph of a SARS-CoV-2 virus particle, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
Seasonal dependence and variation according to climate were expected early in the pandemic due to certain similarities with other human coronavirus diseases; nonetheless, we did not witness a sharp fall in the rates of infections during the summer of 2020, resulting in widespread doubts about COVID-19 seasonality.
Alongside envelope and spike proteins, SARS-CoV-2 also packages the RNA genome encapsidated with manifold copies of nucleocapsid proteins. Moreover, the virus also harbors thousands of copies of the matrix protein. All of this opens the door for constructing virus-like particles (without genetic material) amenable for research.
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.
The value of virus-like particles
In this new paper, researchers from the University of Utah in Salt Lake City and the University of California in Davis (US) have employed atomic force microscopy to investigate the structural stability of individual SARS-CoV-2 virus-like particles at a range of different temperatures – before or after immobilization and drying out on a functionalized glass surface.
"The ability to make virus like particles based on the SARS-CoV-2 genome, combined with abundant available structural information allowing for high precision design strategies opens a unique opportunity for fast progress and allowed us to overcome the safety concerns associated with experiments on the full virus", study authors explain their methodological choice.
In a nutshell, the researchers have utilized this technology to appraise the viral envelope's stability and associated proteins (i.e., matrix, envelope, and spike) under diverse environmental conditions.
The same research group has previously shown that (akin to SARS-CoV) the expression of SARS-CoV-2 matrix, envelope, and spike proteins in transfected human cells is enough for the formation and release of virus-like particles through the same biological pathway that is used by the fully infectious virus.
Viral stability in different temperatures
"We demonstrate that even a mild temperature increase, commensurate with what is common for summer warming, leads to a dramatic disruption of viral structural stability, especially when the heat is applied in the dry state", study authors summarize their findings.
The use of atomic force microscopy revealed that only a handful of SARS-CoV-2 viral particles retain their shape, and even those extraordinary particles degraded almost instantly during scanning, which means they are likely already structurally impaired.
One unexpected finding stemming from this study is how little heating it takes to degrade virus-like particles; more specifically, just 34 °C for as little as 30 minutes was sufficient for a rather dramatic effect. The effect is weaker for particles exposed to elevated temperatures in solution and stronger for exposing them in a dry state.
Conversely, surfaces at 22 °C do not aid in their swift degradation, suggesting that common indoor surfaces and those located outdoors during colder seasons may indeed foster prolonged viral survival and, possibly, increased and extended viral spread.
A single particle perspective on viral seasonality
The results of this study are consistent with other available non-mechanistic studies of viral infectivity and provide a single particle perspective on viral seasonality – consolidating at the same time the case for the resurgence of COVID-19 in the winter.
"It is hard to estimate how all individual contributing factors would contribute to the epidemiological picture on the ground," caution study authors in this exciting bioRxiv paper.
"Nonetheless, our findings draw parallels between the stability of SARS-CoV-2 and the original SARS viruses and add to a growing body of research suggesting more viral spread is likely at lower temperatures via a variety of possible contributing factors", they add.
And since another big wave of the outbreak is looming while we enter the winter season, there is a pressing need to conduct further mechanistic studies of both COVID-19 and the SARS-CoV-2 virus, as these findings will be pivotal for policy decisions.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.