by Alison Ryan

This is an interesting article published 30 January 2020. One of the authors is Thomas Borody, Centre for Digestive Diseases, Sydney, Australia

December 2019, the virus, which would cause a worldwide pandemic, was first identified in the city of Wuhan, China. In January 2020, it was implicated in various pneumonia cases, and was rapidly isolated from a bronchoalveolar lavage sample, analyzed via next-generation sequencing (NGS), and identified to be a novel betacoronavirus, the same family of viruses responsible for severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS).

This new virus, named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on February 11, 2020 by the International Committee on the Taxonomy of Viruses (ICTV), has now been implicated in over 13.4 million cases worldwide, and over 580,000 deaths. Over 138,000 of these deaths have been in the United States alone.

Patients tested PCR positive by nasopharyngeal swab were treated by their primary care physicians with Hydroxychloroquine (HCQ), Azithromycin (Zpack), vitamin C (3000 mg), vitamin D (3000 IU), and zinc (50 mg) for 10 days…5 and 6 days respectively after therapy regimens were initiated patients reported symptom clearance.

Coronaviridae is a family of enveloped, single-stranded, positive-sense RNA viruses. The total length of the genome is 30 Kb, consisting of a 5′-terminal noncoding region, an open reading frame (ORF) 1a/b-coding region, an S region encoding the spike glycoprotein (S protein), an E region encoding the envelope protein (E protein), an M region encoding the membrane protein (M protein), an N region encoding the nucleocapsid protein (N protein), and a 3′-terminal noncoding region. Among them, the poly protein encoded in the ORF1a/b region of the nonstructural protein can be cut by 3CLpro and PLpro of the virus to form RNA-dependent RNA polymerase and helicase, which guides the replication, transcription, and translation of the virus genome. The M and E proteins are involved in the formation of the envelope, while the N protein is involved in assembly. The spike protein which binds to the receptor of the host cell confers specificity for viral invasion into susceptible cells.

Once decoded, the SARS-CoV-2 genome was found to share high sequence identity with the bat coronavirus, BatCoV RaTG13 (96.2%). Upon further investigation, it was discovered that SARS-CoV-2 harbored significant sequence homology with the viruses responsible for SARS and MERS, with a notable exception found in the receptor binding domain (RBD). Shang et al. elucidated the RBD structure of the human of the human ACE2 receptor (angiotensin-converting enzyme 2), demonstrating that the replacement of several residues within the protein caused it to have a much more compact hydrophobic pocket. This change increased the binding affinity of SARS-CoV-2 to ACE2 as compared to SARS-CoV.

While this has contributed to its greater virulence, it also represents a potential therapeutic target…the therapeutic effect of CQ may be a result of its ability to neutralize the endosome-lysosomal acidic pH and block the protease activity necessary for viral entry – possibly evidenced by the HCQ treated patients in this study that appeared to have cleared the virus.

SARS-CoV-2 appears to be mutating at an alarming rate, as reported in the Icelandic study which identified the presence of 291 sequence variants that were not present in the Global Initiative on Sharing All Influenza Data (GISAID) reference database as of March 22, 2020.

Thomas Borody is one of the authors for this study.
Centre for Digestive Diseases, Sydney, Australia
Detection of SARS-CoV-2 from patient fecal samples by whole genome sequencing | Gut Pathogens | Full Text (