Insights on the Mechanical Properties of SARS-CoV-2 Particles and the Effects of the Photosensitizer Hypericin

Abstract

SARS-CoV-2 is a highly pathogenic virus responsible for the COVID-19 disease. It belongs to the Coronaviridae family, characterized by a phospholipid envelope, which is crucial for viral entry and replication in host cells. Hypericin, a lipophilic, naturally occurring photosensitizer, was reported to effectively inactivate enveloped viruses, including SARS-CoV-2, upon light irradiation. In addition to its photodynamic activity, Hyp was found to exert an antiviral action also in the dark. This study explores the mechanical properties of heat-inactivated SARS-CoV-2 viral particles using Atomic Force Microscopy (AFM). Results reveal a flexible structure under external stress, potentially contributing to the virus pathogenicity. Although the fixation protocol causes damage to some particles, correlation with fluorescence demonstrates colocalization of partially degraded virions with their genome. The impact of hypericin on the mechanical properties of the virus was assessed and found particularly relevant in dark conditions. These preliminary results suggest that hypericin can affect the mechanical properties of the viral envelope, an effect that warrants further investigation in the context of antiviral therapies.

Keywords: AFM-fluorescence correlative microscopy; Atomic Force Microscopy (AFM); SARS-CoV-2; enveloped viruses; hypericin; nanomechanical properties; photodynamic therapy (PDT).

Figure 1

Image showing a complete viral particle on a mica surface. Orange arrows point to potential remnants of spike proteins. Scale bar = 50 nm.

Figure 2

Representative fatigue experiment on SARS-CoV-2. The height profiles along the green line for the first (a) and the last (b) images are plotted in panel (c), black and red respectively. Scale bar = 50 nm.

Figure 3

(a) Confocal and (b) AFM images of the same viral particles and (c) detailed image of the particle in the boxed area of panel b, that appears partially damaged. A Gaussian blur was applied to the confocal image, σ = 2. The AFM images were acquired in tapping mode. Scale bar = 200 nm.

Figure 4

(a) QI^TM image of a few viral particles. A dashed square indicates the particle used for the breakthrough measurement reported in (b). Such graph displays the acquired force–distance curve showing visible penetration of the external viral envelope; (c) breakthrough force distributions under three different conditions with [Hyp] = 1 μM, asterisks indicate p value < 0.001.