How SARS-CoV-2 Enters Human Cells & Essential Oils

Understanding how SARS-CoV-2 (enveloped virus) enters human cells is a high priority for deciphering its mystery and curbing its spread. The entry of enveloped viruses into cells is known to occur via two primary pathways: some viruses deliver their genomes to the cytosol after their envelopes fuse with the plasma membrane at the cell surface, whereas others take advantage of the cell's endocytic machinery. In the latter mechanism, the endocytosed virions are subjected to an activation step in the endosome, which is typically mediated by the acidic endosomal pH, resulting in fusion of the viral and endosomal membranes and release of the viral genome into the cytosol. In case of SARS-CoV-2 a virus surface spike protein mediates the virus entry into cells by endocytosis (receptor-dependent endocytosis). To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (angiotensin-converting enzyme 2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Endogenous ACE2 exists at the surface of human cells and is used by the virus to enter these cells by endocytosis where it can multiply. Proteins at the surface of the virus bind ACE2, forming a key and lock system that triggers cell entry (see paper below).

In addition to the spike protein, three other proteins are of elementary importance for the further infection process (virus infection cyle): 3CLpro (virus proteinase), PLpro (virus proteinase), and RdRp (RNA replicase; RNA-dependent RNA polymerase), are essential for the virus (see Figure1).

Figure 1: SARS-Cov-2 life (replication) cycle

SARS-CoV-2 is a single-stranded RNA virus of ~30 kb genome size which belongs to genus Coronavirus and family Coronaviridae. Spike, membrane, and envelope surface viral proteins of coronavirus are embedded in host membrane-derived lipid bilayer encapsulating the helical nucleocapsid comprising viral RNA. Entering of the host cells via the endosomal pathway is followed by the release of viral RNA into the host cytoplasm that undergoes translation and generates replicase polyproteins called pp1a and pp1b that further cleaved by virus encoded proteinases (3CLpro and PLpro) into small proteins. Assembly of virion takes place via interaction of viral RNA and protein at endoplasmic reticulum (ER) and Golgi complex. These virions are subsequently released out of the cells via vesicles (exocytosis) (see below paper).

Patients with COVID-19 show a variety of symptoms associated with respiratory organs such as coughing, sneezing, shortness of breath, and fever. SARS-CoV-2 causes damage to the airway epithelial cells, which means that they are unable to clear the lungs of dirt or mucus, and this can lead to pneumonia. Patients also show evidence of a “cytokine storm”, which are dramatic and damaging increases in levels of chemokine and cytokine proinflammatory molecules, often complicated further by pneumonia. The viruses are transmitted via tiny droplets (or aerosols) that are spread mainly through coughing and sneezing. One third of the patients however also have gastrointestinal symptoms, such as nausea and diarrhea. In addition, the virus can be detected in human stool long after the respiratory symptoms have been resolved. This suggests that the virus can also spread via so-called “fecal-oral transmission.” Researchers from the Hubrecht Institute in Utrecht, Erasmus MC University Medical Center Rotterdam, and Maastricht University in the Netherlands have found that the coronavirus SARS-CoV-2, which causes COVID-19, can infect cells of the intestine and multiply there. These findings could explain the observation that approximately one third of COVID-19 patients experience gastrointestinal symptoms such as diarrhea, and the fact that the virus often can be detected in stool samples. Though the respiratory and gastrointestinal organs may seem very different, there are some key similarities. A particularly interesting similarity is the presence of the ACE2 receptor, the receptor through which the COVID-19 causing SARS-CoV-2 virus can enter the cells. The inside of the intestine is loaded with ACE2 receptors. This finding is also true for other human organs. Similar to SARS-CoV, the extrapulmonary spread of SARS-CoV-2 in humans may be seen due to the widespread tissue expression of the ACE2 receptor.

Essential Oils and Covid19

All statements about essential oils and SARS-CoV-2 must currently be viewed as speculation. The limited research available suggests that enveloped viruses are inactivated by some essential oils and their constituents (e.g. tea tree oil, rosemary oil, thyme oil, oregano oil). In most cases, essential oils and their active ingredients (e.g. eugenol, carvacrol, thymol) interact with the lipid envelope of the cell-free viruses (virions). Electron microscopic studies have shown that the lipid envelope of the virions are destroyed, which means that the virions are no longer able to infect the host cells. This finding can also be applied to SARS Cov-2. This means that the external use of essential oil-containing disinfectants can be a sensible alternative to other conventional disinfectants. You could also mix essential oils and alcohol and use them to make an effective disinfectant (e.g. for hands, body washes, etc.). It would also be conceivable to inhale essential oils as a supportive treatment as part of comprehensive physical hygiene measures, such as keeping your distance, washing your hands and wearing a nasal mask.

Interestingly, it has recently been shown that individual components of essential oils can interact with important target structures of the virus replication cycle (virus life cycle) (e.g. isothymol with ACE2 receptors of the host cell or 1,8-cineol with the viral proteinases such as 3CLpro). These first in vitro findings could be important for future studies on the anti-CoV-2 effects of essential oils and their components. These studies show that individual components of essential oils have the potential to inhibit virus replication, at least in vitro.

It is hoped that clinical studies will soon show that essential oils are indeed antiviral agents in vivo and not just remain vague promises.

By Dr. Jürgen Reichling, IFA Specialist Advisor
 

Further Reading

• Morphology, Genome Organization, Replication, and Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
• Cell entry mechanisms of SARS-CoV-2