SARS‑Cov‑2 D614G Spike Protein Mutation is Associated with Potentially Higher viral load in COVID-19 Patients

2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Pratap Singh
Keyword(s):  
Viral Load ◽  
Spike Protein ◽  
Protein Mutation

scholarly journals Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation

2021 ◽  
Author(s):  
Xianding Deng ◽  
Miguel A Garcia-Knight ◽  
Mir M. Khalid ◽  
Venice Servellita ◽  
Candace Wang ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Cell Cultures ◽  
Spike Protein ◽  
Nasopharyngeal Swab ◽  
Whole Genome ◽  
Wild Type ◽  
Antibody Neutralization ◽  
Protein Mutation ◽  
Viral Shedding

AbstractWe identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.

scholarly journals Long period dynamics of viral load and antibodies for SARS-CoV-2 infection: an observational cohort study

2020 ◽  
Author(s):  
Jianping Huang ◽  
Tingting Mao ◽  
Shufei Li ◽  
Lianpeng Wu ◽  
Xueqin Xu ◽  
...  
Keyword(s):  
Viral Load ◽  
Acute Phase ◽  
Symptom Onset ◽  
Viral Persistence ◽  
Viral Rna ◽  
Spike Protein ◽  
Peak Time ◽  
Protective Antibody ◽  
Long Period ◽  
Long Time

ABSTRACTOBJECTIVETo investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period.DESIGNRetrospective, observational case series.SETTINGWenzhou Sixth People’s HospitalPARTICIPANTSThirty-three patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to hospital. Data were collected from January 27 to April 10, 2020.MAIN OUTCOME MEASURESThroat swabs, sputum, stool, and blood samples were collected, and viral load was measured by reverse transcription PCR (RT-PCR). Specific IgM and IgG against spike protein (S), spike protein receptor binding domain (RBD), and nucleocapsid (N) were analyzed.RESULTSAt the early stages of symptom onset, SARS-CoV-2 viral load is higher in throat swabs and sputum, but lower in stool. The median (IQR) time of undetectable viral RNA in throat swab, sputum, and stool was 18.5 (13.25-22) days, 22 (18.5-27.5) days, and 17 (11.5-32) days, respectively. In sputum, 17 patients (51.5%) had undetectable viral RNA within 22 days (short persistence), and 16 (48.5%) had persistent viral RNA more than 22 days (long persistence). Three patients (9.1%) had a detectable relapse of viral RNA in sputum within two weeks of their discharge from the hospital. One patient had persistent viral RNA for 59 days or longer. The median (IQR) seroconversion time of anti-S IgM, anti-RBD IgM, and anti-N IgM was 10.5 (7.75-15.5) days, 14 (9-24) days, and 10 (7-14) days, respectively. The median (IQR) seroconversion time of anti-S IgG, anti-RBD IgG, and anti-N IgG was 10 (7.25-16.5) days, 13 (9-17) days, and 10 (7-14) days, respectively. By week 8 after symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels were 4-times higher in convalescence than in acute phase. SARS-CoV-2 RNA coexisted with antibodies for more than 50 days. Anti-RBD IgM and IgG levels, including anti-RBD IgM levels at presentation and peak time, were significantly higher in viral RNA short persistence patients than in long persistence patients.CONCLUSIONThis study adds important new information about the features of viral load and antibody dynamics of SARS-CoV-2. It is clear from these results that the viral RNA persists in sputum and stool specimens for a relatively long time in many patients. Anti-RBD may also serve as a potential protective antibody against SARS-CoV-2 infection, as viral persistence appears to be related to anti-RBD levels. Earlier treatment intervention also appears to be a factor in viral persistence.WHAT IS ALREADY KNOWN ON THIS TOPICThere are several reports about the serum antibodies against SARS-CoV-2. However, most of them evaluate diagnostic accuracy. Only two articles report dynamics of SARS-CoV-2 viral RNA and antibodies with serial samples, but the observation periods are within 30 days. None of the studies investigate the profiles of SARS-CoV-2 viral load and antibodies in a long period. Three reports investigate profiles in respiratory samples, but there are no reports on the dynamics of the viral load in stool samples.WHAT THIS STUDY ADDSIn both sputum and stool, SARS-CoV-2 RNA persists for a long time. The anti-RBD antibodies may involve in the clearance of SARS-CoV-2 infection. After eight weeks from symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels increased 4-time higher in convalescence than in acute phase. Long persistence of SARS-CoV-2 viral RNA in sputum and stool presents challenges for management of the infection. The IgM/IgG comb test is better than single IgM test as a supplement diagnostic tool. Anti-RBD may be a protective antibody, and is valuable for development of vaccines.

scholarly journals Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques

2021 ◽  
Author(s):  
Neeltje van Doremalen ◽  
Jyothi N. Purushotham ◽  
Jonathan E. Schulz ◽  
Myndi G. Holbrook ◽  
Trenton Bushmaker ◽  
...  
Keyword(s):  
Viral Load ◽  
Animal Models ◽  
Respiratory Tract ◽  
Bronchoalveolar Lavage ◽  
Lung Tissue ◽  
Lower Respiratory Tract ◽  
Infectious Virus ◽  
Rhesus Macaques ◽  
Spike Protein ◽  
Transmission Model

AbstractIntramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 protected rhesus macaques against pneumonia but did not reduce shedding of SARS-CoV-2. Here we investigate whether intranasally administered ChAdOx1 nCoV-19 reduces shedding, using a SARS-CoV-2 virus with the D614G mutation in the spike protein. Viral load in swabs obtained from intranasally vaccinated hamsters was significantly decreased compared to controls and no viral RNA or infectious virus was found in lung tissue, both in a direct challenge and a transmission model. Intranasal vaccination of rhesus macaques resulted in reduced shedding and a reduction in viral load in bronchoalveolar lavage and lower respiratory tract tissue. In conclusion, intranasal vaccination reduced shedding in two different SARS-CoV-2 animal models, justifying further investigation as a potential vaccination route for COVID-19 vaccines.

scholarly journals AUG-3387, a Human-Derived Monoclonal Antibody Neutralizes SARS-CoV-2 Variants and Reduces Viral Load from Therapeutic Treatment of Hamsters In Vivo

2021 ◽  
Author(s):  
Christopher J Emig ◽  
Marco A Mena ◽  
Steven J Henry ◽  
Adela Vitug ◽  
Christian John Ventura ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Viral Load ◽  
Human Monoclonal Antibody ◽  
Dry Powder Inhaler ◽  
Spike Protein ◽  
Geometric Standard Deviation ◽  
Human Populations ◽  
Dry Powder ◽  
Powder Formulation

Infections from the SARS-CoV-2 virus have killed over 4.6 million people since it began spreading through human populations in late 2019. In order to develop a therapeutic or prophylactic antibody to help mitigate the effects of the pandemic, a human monoclonal antibody (mAb) that binds to the SARS-CoV-2 spike protein was isolated from a convalescent patient following recovery from COVID-19 disease. This mAb, designated AUG-3387, demonstrates a high affinity for the spike protein of the original viral strains and all variants tested to date. In vitro pseudovirus neutralization and SARS-CoV-2 neutralization activity has been demonstrated in vitro. In addition, a dry powder formulation has been prepared using a Thin Film Freezing (TFF) process that exhibited a fine particle fraction (FPF) of 50.95 ± 7.69% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 3.74 ± 0.73 μm and 2.73 ± 0.20, respectively. The dry powder is suitable for delivery directly to the lungs of infected patients using a dry powder inhaler device. Importantly, AUG-3387, administered as a liquid by intraperitoneal injection or the dry powder formulation delivered intratracheally into Syrian hamsters 24 hours after intranasal SARS-CoV-2 infection, demonstrated a dose-dependent reduction in the lung viral load of the virus. These data suggest that AUG-3387 formulated as a dry powder demonstrates potential to treat COVID-19.

scholarly journals N‐terminal domain of SARS CoV‐2 spike protein mutation associated reduction in effectivity of neutralizing antibody with vaccinated individuals

2021 ◽  
Author(s):  
Yogendar Singh ◽  
Neeraj Kumar Fuloria ◽  
Shivkanya Fuloria ◽  
Vetriselvan Subramaniyan ◽  
Dhanalekshmi Unnikrishnan Meenakshi ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Spike Protein ◽  
Protein Mutation ◽  
Terminal Domain

scholarly journals Gene Expression of ECA2 Receptors in the Oral Cavity and Salivary Glands and Its Role in SARS CoV2 Infection. Literature Review

2020 ◽  
pp. 245-250
Author(s):  
Francisco Germán Villanueva-Sánchez ◽  
Karla Mayela Avelar-Juárez ◽  
Nancy Pérez-Cornejo ◽  
Eduardo Alonso Cruz-Monroy ◽  
José David Ramos-Baena
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
Literature Review ◽  
Oral Cavity ◽  
Salivary Glands ◽  
Host Cell ◽  
Health Personnel ◽  
Spike Protein ◽  
Squamous Cells ◽  
Dental Professionals

ECA2 receptors have an important gene expression in the squamous cells of the tongue and salivary glands, a mechanism that is convenient for the inoculation of SARS CoV2 since it seeks to make the assembly complex through its glycoprotein or spike protein towards the ECA2 receptor of the oral mucosa. Once inoculated and favored by proteases, it is the key that allows the entry of the virion into the host cell for its subsequent replication, increase of viral load and potential deamination and infection; dental professionals must be alert to the mechanisms of infection in the oral cavity for their own protection and that of the patients who are treated by this health personnel.

scholarly journals Abundant transmission of Corona Virus Nsp2 RNA Topoisomerse I120F Mutants with Concurrence D614G Spike Protein Mutation in Australia

2021 ◽  
Author(s):  
ASIT KUMAR CHAKRABORTY
Keyword(s):  
Amino Acid ◽  
Topoisomerase I ◽  
Sequence Similarity ◽  
Virus Transmission ◽  
Spike Protein ◽  
Virus Protein ◽  
Dna Topoisomerase ◽  
Amino Acid Homology ◽  
Protein Mutation ◽  
Corona Virus

We previously predicted Nsp2 Corona virus protein as RNA topoisomerase through amino acid homology among Vibrio haemolytica DNA topoisomerase IA/IV as well as DNA primase, DNA gyrase and bi-subunit Trypanosoma brucei DNA topoisomerase IB. Many DNA topoisomerase I/III have RNA topoisomerase activity and such ubiquitous enzymes are conserved and involved in the regulation of replication and transcription. We have checked here mutational profile of Nsp2 RNA topoisomerase analyzing >10000 orf1a 4405 amino acid length Corona virus polyprotein. Mutant proteins were selected by BLAST search having 99.84% sequence similarity and 181-818aa portion Nsp2 protein (protein id. QIU82057) was analyzed using CLUSTAL Omega software. We found 26 different mutations where most changes were selected at Isoleucine and Alanine into Valine or Leucine into Phenylanaline pinpointing conserved nature of the Corona virus RNA topoisomerase. Major nonsense very abundant mutations were found at I120F (Isoleucine to Phenylalanine). Other important mutations were R27C, I198V, T85I, L410F, I559V and P583S. The I120F mutation was abundant in Australian isolates and its spread was seen in the Bangladesh and other countries like USA. We suggest that abundant I120F mutation of Nsp2 Topoisomerase may increase transmission of Corona virus by stabilizing RNA structure for efficient virus pakaging. Interestingly, such mutations were found in association of D614G mutation of Spike protein, known to >70% increase infectivity. On the contrary, all P583S Nsp2 mutants analyzed had no concurrence D614G spike protein mutation. Many silent mutations (5-7) were detected by genome wide analysis but no N501Y Spike protein mutation. This is first report that predicts a link of greater Corona virus transmission with Nsp2 protein I120F and spike protein D614G mutations.

scholarly journals Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sandra Isabel ◽  
Lucía Graña-Miraglia ◽  
Jahir M. Gutierrez ◽  
Cedoljub Bundalovic-Torma ◽  
Helen E. Groves ◽  
...  
Keyword(s):  
Spike Protein ◽  
Protein Mutation

scholarly journals Spike Protein NTD mutation G142D in SARS-CoV-2 Delta VOC lineages is associated with frequent back mutations, increased viral loads, and immune evasion

2021 ◽  
Author(s):  
Lishuang Shen ◽  
Timothy J. Triche ◽  
Jennifer Dien Bard ◽  
Jaclyn A. Biegel ◽  
Alexander R. Judkins ◽  
...  
Keyword(s):  
Viral Load ◽  
Immune Evasion ◽  
Neutralizing Antibodies ◽  
Amino Acid Position ◽  
Spike Protein ◽  
Multiple Time ◽  
Viral Neutralization ◽  
Antibody Recognition ◽  
Recurrent Mutations ◽  
Multiple Time Points

AbstractThe significantly greater infectivity of the SARS-CoV-2 Delta variants of concern (VOC) is hypothesized to be driven by key mutations that result in increased transmissibility, viral load and/or evasion of host immune response. We surveyed the mutational profiles of Delta VOC genomes between September 2020 and mid-August 2021 and identified a previously unreported mutation pattern at amino acid position 142 in the N-terminal domain (NTD) of the spike protein which demonstrated multiple rounds of mutation from G142 to D142 and back. This pattern of frequent back mutations was observed at multiple time points and across Delta VOC sub-lineages. The etiology for these recurrent mutations is unclear but raises the possibility of host-directed editing of the SARS-CoV-2 genome. Within Delta VOC this mutation is associated with higher viral load, further enhanced in the presence of another NTD mutation (T95I) which was also frequently observed in these cases. Protein modeling of both mutations predicts alterations of the surface topography of the NTD by G142D, specifically disturbance of the ‘super site’ epitope that binds NTD-directed neutralizing antibodies (NAbs). The appearance of frequent and repeated G142D followed by D142G back mutations is previously unreported in SARS-CoV-2 and may represent viral adaptation to evolving host immunity characterized by increasing frequency of spike NAbs, from both prior infection and vaccine-based immunity. The emergence of alterations of the NTD in and around the main NAb epitope is a concerning development in the ongoing evolution of SARS-CoV-2 which may contribute to increased infectivity, immune evasion and ‘breakthrough infections’ characteristic of Delta VOC. Future vaccine and therapy development may benefit by recognizing the emergence of these novel spike NTD mutations and considering their impact on antibody recognition, viral neutralization, infectivity, replication, and viral load.

scholarly journals Association of E484K spike protein mutation with SARS-CoV-2 infection in vaccinated persons---Maryland, January – May 2021

2021 ◽  
Author(s):  
Kenneth A Feder ◽  
Ami Patel ◽  
Venkata R Vepachedu ◽  
Catherine Dominguez ◽  
Eric N Keller ◽  
...  
Keyword(s):  
Spike Protein ◽  
Protein Mutation ◽  
Adjusted Analysis

Abstract Among 9,048 people infected with SARS-CoV-2 between January-May, 2021 in Maryland, in regression-adjusted analysis, SARS-CoV-2 viruses carrying the spike protein mutation E484K were disproportionately prevalent among persons infected after full vaccination against COVID-19 as compared to infected persons who were not fully vaccinated (aOR 1.96, 95% CI, 1.36 to 2.83).

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