The impact of super-spreaders in COVID-19: mapping genome variation worldwide

Gómez-Carballa, Alberto; Bello, Xabier; Pardo-Seco, Jacobo; Martinón-Torres, Federico; Salas, Antonio

doi:10.1101/2020.05.19.097410

Cited by 12 publications

(23 citation statements)

References 47 publications

(18 reference statements)

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“…and America have been the most affected regions, accounting for almost 80% of worldwide cases and deaths [2]. Despite SARS-CoV-2 strains having a within-sequence identity of 99.98%, it has been classified in 2 haplogroups (A and B), the first being the predominant worldwide and the second being more prevalent in America and Asia than in Africa and Europe [3]. Nevertheless, it remains unclear whether the severity and outcome of the disease are related to the virus strain.…”

Section: Introductionmentioning

confidence: 99%

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment

Gąsecka

Borovac

Guerreiro

et al. 2020

Cardiovasc Drugs Ther

117

120

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Introduction Emerging evidence points to an association between severe clinical presentation of COVID-19 and increased risk of thromboembolism. One-third of patients hospitalized due to severe COVID-19 develops macrovascular thrombotic complications, including venous thromboembolism, myocardial injury/infarction and stroke. Concurrently, the autopsy series indicate multiorgan damage pattern consistent with microvascular injury. Prophylaxis, diagnosis and treatment COVID-19 associated coagulopathy has distinct features, including markedly elevated D-dimers concentration with nearly normal activated partial thromboplastin time, prothrombin time and platelet count. The diagnosis may be challenging due to overlapping features between pulmonary embolism and severe COVID-19 disease, such as dyspnoea, high concentration of D-dimers, right ventricle with dysfunction or enlargement, and acute respiratory distress syndrome. Both macro- and microvascular complications are associated with an increased risk of in-hospital mortality. Therefore, early recognition of coagulation abnormalities among hospitalized COVID-19 patients are critical measures to identify patients with poor prognosis, guide antithrombotic prophylaxis or treatment, and improve patients’ clinical outcomes. Recommendations for clinicians Most of the guidelines and consensus documents published on behalf of professional societies focused on thrombosis and hemostasis advocate the use of anticoagulants in all patients hospitalized with COVID-19, as well as 2-6 weeks post hospital discharge in the absence of contraindications. However, since there is no guidance for deciding the intensity and duration of anticoagulation, the decision-making process should be made in individual-case basis. Conclusions Here, we review the mechanistic relationships between inflammation and thrombosis, discuss the macrovascular and microvascular complications and summarize the prophylaxis, diagnosis and treatment of thromboembolism in patients affected by COVID-19.

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Section: Introductionmentioning

confidence: 99%

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment

Gąsecka

Borovac

Guerreiro

et al. 2020

Cardiovasc Drugs Ther

117

120

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“…RNA viruses display a characteristic feature of high mutability and with no exception, SARS-CoV-2 being a positive strand RNA virus has been evolving at a rapid rate since its emergence in Wuhan during the end of 2019. In the span of six months (December, 2019-June, 2020), the circulating SARS-CoV-2 strains have accumulated a large number of mutations which might result in altered virulence, infectivity and transmissibility [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…mutational analysis of 441 Indian SARS-CoV-2 strains identified in different geographical regions of India, and classified them on the basis of co-existing mutations.Our data highlighted the existence of 33 different mutations (32 mutations in 9 different protein coding genes and 1 in 5"-UTR) among Indian SARS-CoV-2 strains. Maximum number of mutations were detected in S protein (8) followed by NSP3 (7), NSP12 (5), NSP2(4), N (3) and NSP4(2). Only single mutation has been observed in 5"-UTR, NSP6, ORF3a and ORF8 gene segments.…”

mentioning

confidence: 99%

Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: An endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations

Sarkar

Mitra

Chandra

et al. 2020

Preprint

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Accumulation of mutations within the genome is the primary driving force for viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility as well as antigenic shift to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we aimed at genome-wide analyses of circulating SARS-CoV-2 viruses for the emergence of novel co-existing mutations and trace their spatial distribution within India. Comprehensive analysis of whole genome sequences of 441 Indian SARS-CoV-2 strains revealed the occurrence of 33 different mutations, 21 being distinctive to India. Emergence of novel mutations were observed in S glycoprotein (7/33), NSP3 (6/33), RdRp/NSP12 (4/33), NSP2 (2/33) and N (2/33). Non-synonymous mutations were found to be 3.4 times more prevalent than synonymous mutations. We classified the Indian isolates into 22 groups based on the co-existing mutations. Phylogenetic analyses revealed that representative strain of each group divided themselves into various sub-clades within their respective clades, based on the presence of unique co-existing mutations. India was dominated by A2a clade (55.60%) followed by A3 (37.38%) and B (7%), but exhibited heterogeneous distribution among various geographical regions. The A2a clade mostly predominated in East India, Western India and Central India, whereas A3 clade prevailed in South and North India. In conclusion, this study highlights the divergent evolution of SARS-CoV-2 strains and co-circulation of multiple clades in India. Monitoring of the emerging mutations would pave ways for vaccine formulation and designing of antiviral drugs.

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“…An analysis of the genomic sequences from >4000 SARS-CoV2 isolates located 36 mutations at the nsp7 protein sequence. Only 27% of the mutations were missense mutations and most of those were conservative ( Figure 2) [7].…”

Section: Characteristics Of the Nsp7 Structural Models Selected For Tmentioning

confidence: 99%

In silico screening for natural ligands to non-structural nsp7 conformers of SARS coronaviruses

Blasco¹,

Coll

2020

Preprint

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<p>The non-structural protein 7 (nsp7) of Severe Acute Respiratory Syndrome (SARS) coronaviruses was selected as a new target to potentially interfere with viral replication. The nsp7s are uniquely conserved small coronavirus proteins having a critical, yet intriguing participation on the replication of the long viral RNA genome after complexing with nsp8 and nsp12. Drugs with potential to interfere with nsp7s have not been described yet. Despite the difficulties of having no previously defined binding pocket, high-throughput blind screening of more than one hundred thousand natural compounds < 400 Dalton of molecular weight docked against the nsp7.1ysy conformer identified hundreds of leads displaying predicted high binding-affinities by AutoDockVina. The leads were then docked to 14 nsp7 available conformers by two different binding scoring algorithms ( AutoDockVina-PyRx and HYDE-seeSAR), to identify consensus top-leads. Further predictive analysis of their physiological/toxicity ADMET criteria (chemical properties, adsorption, metabolism, toxicity) narrowed top-leads to a few drug-like ligands, most of them showing steroid-like structures closely related to some of those being actually used in clinical work. A final optimization by search for structural similarities to the drug-like top-lead, yielded a collection of novel steroid-like ligands with ~100-fold higher-affinity whose antiviral activity may be experimentally validated since they are available. Additionally, these nsp7-interacting ligands and/or their further optimized derivatives, may offer new tools to investigate the intriguing role of nsp7 on replication of coronaviruses<br></p>

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The impact of super-spreaders in COVID-19: mapping genome variation worldwide

Cited by 12 publications

References 47 publications

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment

Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: An endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations

In silico screening for natural ligands to non-structural nsp7 conformers of SARS coronaviruses

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