Advances in SARS-Cov-2 Biology

Using SARS-CoV-2-specific antibody- and neutralization assays, Dogan et al find that hospitalized individuals show higher IgG antibody responses and higher neutralization titers compared to outpatient or convalescent plasma donors, providing insights into the host humoral response to SARS CoV-2.

Lili Ren et al. investigate antibody response from 176 COVID-19 patients who presented different stages of their disease. This study suggests the late onset of antibody response as a risk factor for disease severity and a limited role of antibody titers in predicting the disease severity of COVID-19.

Rosa et al. find that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are induced in the lungs of macaques in response to SARS-CoV-2 infection, whereas genes associated with collagen formation and regulation are reduced. Authors also note an overlap of genes associated with SARS-CoV-2 infection and tuberculosis, altogether providing new insights into the immunopathogenesis of COVID-19 disease.

Sannigrahi et al. discuss conformational switching that allows proteins to alter their conformation, aiding in pathogenesis by enabling cellular entry of viruses and bacterial toxins. Focussing on fusion domain of the Spike glycoprotein of SARS COV2 virus, they identify similar “switching sequences” present in diverse pathogen derived proteins.

Rong Xu, Renfei Lu, Tao Zhang, Qunfu Wu, and colleagues perform a longitudinal analysis of throat and gut microbiomes on adult COVID-19 patients. They find initially lower bacterial diversity in COVID-19 patients, but demonstrate a restoration of microbiome diversity throughout disease progression for patients with mild forms of the disease.

Amanda Melin et al. compare variation in 29 primate species at 12 amino acid residue sites coded by the ACE2 gene and show that apes and African and Asian monkeys exhibit the same set of twelve key amino acid residues as human ACE2. These results suggest that these primates are likely to be susceptible to SARS-CoV-2, whereas ACE2 gene sequences and protein-protein interaction models suggest reduced susceptibility for platyrrhines, tarsiers, lorisoids, and some lemurs.

Lv et al. associate the gut mycobiota with clinical features and the bacterial microbiota by comparing COVID-19 patients to those infected with H1N1 and healthy controls. They find that gut mycobiota dysbiosis occurs in both COVID-19 patients and those infected with H1N1 and that it does not improve until patients no longer require medical attention, providing insights into a better healthcare guideline.

Iain MacLeod et al. develop the Pan-Degenerate Amplification and Adaptation (PANDAA) point mutation assay to detect HIV drug resistance mutations. This method can be applied to any pathogen where target-proximal genetic variability hinders diagnostic development.

Samarakoon et al. present Genopo, a portable toolkit for analysis of nanopore sequencing data on Android smartphone and tablet devices. Genopo enables field-based nanopore analysis using widely accessible technology.

Mohan, Abdulhalim and Cvelbar investigated the capabilities of different plasmonic-based sensing techniques including the surface plasmon resonance (SPR), localised SPR, surface-enhanced Raman scattering (SERS), surface-enhanced fluorescence (SEF) and surface-enhanced infrared absorption spectroscopy (SEIRA) for the detection of viruses. The presented data will assist in the development of novel and versatile virus biosensors.

Mishra, Huang et al. identify 29 linear SARS-CoV-2 epitopes that are immunoreactive with the plasma from individuals who had asymptomatic, mild, or severe SARS-CoV-2 infections. This study suggests the possibility of using these peptides to discriminate the exposure to SARS-CoV-2 and other human coronaviruses.

Liang, Gu and other colleagues develop a convoluted neural network (CNN)-based framework to diagnose COVID-19 infection from chest X-ray and computed tomography images, and comparison with other upper respiratory infections. Compared to expert evaluation of the images, the neural network achieved upwards of 99% specificity, showing promise for the automated detection of COVID-19 infection in clinical settings.

Egia-Mendikute et al. develop a multiplexed flow cytometric bead array to simultaneously detect antibodies reactive to three immunogenic SARS-CoV-2 proteins. More sensitive than ELISA, they detected N-reactive antibodies in COVID-19-negative individuals with this assay, showing it to have superior potential to detect low antibody titres compared to current gold standard serology methods.

Karoyan et al. present a method to inhibit SARS-CoV-2 by means of a peptide-mimic approach. They design a series of peptides mimicking the N-terminal helix of hACE2 protein and their best peptide-mimic blocks SARS-CoV-2 human pulmonary cell infection with an IC50 in nanomolar range.

Youngchang Kim, Jacek Wower, and colleagues explore the sequence specificity, metal ion dependence and catalytic mechanism of the Nsp15 endoribonuclease NendoU from SARS-CoV-2. The authors also solve five new crystal structures of the enzyme in complex with 5’UMP, 3’UMP, 5’cGpU, uridine 2′,3′-vanadate (transition state analog) and Tipiracil (uracil mimic), and demonstrate that Tipiracil inhibits SARS-CoV-2 Nsp15 by interacting with the uridine binding pocket in the enzyme’s active site.

Deng-hai Zhang et al. report a network pharmacology analysis of the Traditional Chinese Medicine (TCM) lung-cleaning and toxicity-excluding (LCTE) soup. By exploring the chemical compounds that make up LCTE and the likely pathways and proteins that they target, the authors show that LCTE may have the potential to directly inhibit the SARS-CoV-2 virus and relieve inflammatory symptoms.

Pranam Chatterjee et al. present a novel computational platform for engineering peptide fusions that bind to the SARS-CoV-2 spike protein and tag it for proteasomal degradation. They experimentally validate an optimal variant in human cells, showing that it inhibits production of infection-competent virus.

Gontu et al. conducted a longitudinal study in COVID patients in which they assessed the response trajectories of antibodies directed to the SARS-CoV-2 surface spike glycoprotein and in vitro SARS-CoV-2 live virus neutralizing titers. Their measurements demonstrate the presence of an optimum window for convalescent plasma donation as well as predictions of the most suitable donor type.

Here, the authors identify potential drugs that target 3-chymotrypsin like protease (3CLpro), which is a pivotal protease for the replication of SARS-CoV-2. They found that off-target inhibitors such as ivermectin and micafungin inhibit 3CLpro enzyme activity, suggesting that these molecules could constitute useful therapies to inhibit SARS-CoV-2 replication.

Song et al describe and identify monoclonal antibodies that target the SARSCoV-2 Spike protein, including CA521FALA, which demonstrated neutralising potential in vivo and in vitro. They performed structural analysis, which revealed that CA521FALA recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 Spike protein therefore making it a promising therapeutic antibody.

Dimple Chakravarty et al. review the rapidly emerging data indicating a higher rate of SARS-CoV-2 infection in men. They note that men in the age group most at risk of infection are also at high risk of prostate cancer, and explore the potential links between these diseases and implications for COVID-19 treatment in prostate cancer patients.

Wenzhong Shi et al. propose an extended Weight Kernel Density Estimation model to predict the COVID-19 onset risk, with and without the Wuhan lockdown, and corresponding symptom onset and spatial heterogeneity in 347 Chinese cities. The authors find that the lockdown delayed COVID-19 peak onset by 1–2 days and decreased onset risk by up to 21%.

Ives and Bozzuto estimate the spread rate of COVID-19 in the USA at the start of the epidemic, extrapolating values of R₀ for 3109 counties during the period before measures were taken to reduce the spread. Most of predictive variation in county-level values of R₀ is explained by population density and spatial location, with differences among locations associated with differences among strains of SARS-CoV-2.

Rui Wang et al. report a comprehensive analysis of nearly 13,000 SARS-CoV-2 genome sequences isolated from patients in the United States, comprising more than 7000 single mutations. They show that SARS-CoV-2 genomes cluster into four distinct groups and that two of these groups are potentially more infectious, underlining the urgent need for viral control strategies in the US.

Giovanetti et al. examine SARS-CoV-2 transmission dynamics in Italy using phylodynamic analysis of viral genetic and epidemiological data. They present evidence to suggest that the efficacy of public health interventions is limited by the size and structure of epidemic reservoirs, which may influence vaccination programmes.