SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets

Abstract

The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.

Keywords: Brain; COVID-19; Diabetes mellitus; Multiple sclerosis; Neutralizing antibodies; SARS-CoV-2; Therapeutics.

Graphical abstract

Fig. 1

Route of Transmission of CoVs in to humans: a. SARS-CoV; Primary source is Bats and Civet Cats are intermediate reservoirs; b) MERS-CoV; Primary source is Bats and Camels are intermediate reservoirs; c) COVID-19; Primary source is Bats and Pangolins are intermediate reservoirs (putative).

Fig. 2

The number cases and deaths data was taken from WHO (https://who.sprinklr.com/) and CDC till May 14th, 2020. The Case Fatality was calculated as the ration of No. of Confirmed Covid-19 cases over No. of Covid-19 deaths. However, Case fatality rate is low for SARS-CoV2 (3–4%) in comparison with SARS-CoV (9.6%), MERS-CoV (34%). Case fatality rate Source from https://www.worldometers.info/coronavirus/coronavirus-death-rate/

Fig. 3

a) Structure of SARS-CoV2: Labeled with spike proteins, M-proteins, HE, E, and RNA with Nucleocapsid (N) proteins. b) Transmission electron microscopic (TEM) images- SARS-CoV2 marked with arrow head, image credit: Centers for Disease Control and Prevention (CDC)|CS Goldsmith and TG Ksiazek (left) and NIAID (right). c). Colored TEM with predominant spike proteins on envelope of SARS-CoV2 (COVID-19), image credit: NIAID-RML/NATIONAL INSTITUTES OF HEALTH/SCIENCE PHOTO LIBRARY.

Fig. 4

Genome of SARS-CoV2 originated in china: SARS-CoV2 (IVDC-HB-01/2019 (HB01) strain) RNA genome organization with pp1ab and pp1a proteins. The “orf1ab” is the largest gene, and it encodes for the “pp1ab” protein; contains nsp1-nsp10 and nsp12-nsp16 (15 nsps); another protein “pp1a” protein (coded by orf1a) contains nsp1-nsp10 (10 nsps). Structural proteins are encoded by the four structural genes, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) genes. NSPS; non structural protein sequence, Orf; Open reading frame Credit: Adapted from Wu et al., Cell Host Microbe. 2020 Mar 11;27(3):325–328.

Fig. 5

Pathophysiology of SARS-CoV2.