Potential Fast COVID-19 Containment With Trehalose

Abstract

Countries worldwide have confirmed a staggering number of COVID-19 cases, and it is now clear that no country is immune to the SARS-CoV-2 infection. Resource-poor countries with weaker health systems are struggling with epidemics of their own and are now in a more uncertain situation with this rapidly spreading infection. Frontline healthcare workers are succumbing to the infection in their efforts to save lives. There is an urgency to develop treatments for COVID-19, yet there is limited clinical data on the efficacy of potential drug treatments. Countries worldwide implemented a stay-at-home order to "flatten the curve" and relieve the pressure on the health system, but it is uncertain how this will unfold after the economy reopens. Trehalose, a natural glucose disaccharide, is known to impair viral function through the autophagy system. Here, we propose trehalose as a potential preventative treatment for SARS-CoV-2 infection and transmission.

Keywords: COVID-19; SARS-CoV-2; autophagy; prophylaxis; trehalose.

Figure 1

SARS-CoV2 replication and inhibition by trehalose. SARS-CoV-2 gains entry via membrane fusion by binding angiotensin-converting enzyme 2 (ACE2) in the target cell. The virus is then internalized and transported through endosomal compartments. The viral genome is released and used by the host ribosome to synthesize viral RNA polymerase, thus replicating the viral RNA subgenomes. Viral structural proteins are synthesized and anchored into the endoplasmic reticulum (ER). Once the virion is assembled in the ER-Golgi intermediate compartment (ERGIC) and transferred to the autophagosome, it may be released by exocytosis from the amphisome. Coronavirus nonstructural protein 6 (nsp6) and nsp3 promote autophagosome formation but prevent autophagosome-lysosome fusion. (1) Trehalose may promote amphisome-lysosome fusion for virion degradation after the trafficking of viral double-membrane vesicles. (2) Trehalose can also activate transcription factor EB (TFEB) and promote lysosome biogenesis.

Figure 2

Trehalose treatment for fast SARS-CoV-2 containment. Treating healthy adults and asymptomatic patients with trehalose would accelerate community viral containment.