Evaluating the trade-off between transmissibility and virulence of SARS-CoV-2 by mathematical modeling

Hm, Yang; Junior, Lombardi; Ac, Yang

doi:10.1101/2021.02.27.21252592

Cited by 4 publications

(8 citation statements)

References 11 publications

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“…Using the next generation matrix theory to the trivial equilibrium point P 0 , and applying the method proposed in [15] and proved in [16], we obtained the basic reproduction number R 0 given by R 0 = (R 1y + R 2y ) s 0 y + (R 1o + R 2o ) s 0 o , (A. 6) where the partial basic reproduction numbers R 1y , R 2y , R 1o , and R 2o are given by equation (12) in the main text, and the initial fractions are s 0 y = φ/ (φ + ϕ) and s 0 o = ϕ/ (φ + ϕ). Details can be found in [5].…”

Section: Discussionmentioning

confidence: 99%

“…with Ω(0) = 0, (6) which are the exit from class P , and entering into class D. To evaluate Ω, the numerical solutions of equations ( 1), ( 2) and ( 3) are obtained using the initial conditions given by equation (A.3) in Appendix A. We search for the value of x minimizing the Sum.…”

Section: Methodsmentioning

confidence: 99%

“…Another effect of higher virulence is the increased amount of virus released by infectious individuals in the environment, which must increase the transmission [8]. However, the isolation of severe and part of mild CoViD-19 cases decreases the transmission populationally [6].…”

Section: Methodsmentioning

confidence: 99%

“…However, all compartments' values are not changed when mutations occur, and more virulent variant circulates. In this case only the parameter related to the virulence l y and l o are varied [6].…”

Section: Phases 3 Andmentioning

confidence: 99%

“…At the end of June 2020, just after the peak of the epidemic under isolation [5], the relaxation was initiated but not fully implemented. The continuous transmission of SARS-CoV-2 may result in the appearance of more virulent variants, which explains the increased CoViD-19 fatalities compared with the epidemic with less virulent ones [6]. São Paulo State associated the variant P.1 with increased mortality in the CoViD-19 epidemic, as observed in the Amazonas State [7].…”

Section: Introductionmentioning

confidence: 96%

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Quarantine, relaxation and mutation explaining the CoViD-19 epidemic in São Paulo State (Brazil)

Hm¹,

Lpp

Ffm

et al. 2021

Preprint

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Background: The continuous SARS-CoV-2 transmission in several countries could contribute to the mutations' appearance. The circulation of more virulent variants may increase the number of severe CoViD-19 needing hospital care and fatalities hugely. Methods: The partial quarantine in São Paulo State and further relaxation associated with the mutations are explained by a mathematical model based on the CoViD-19 natural history encompassing the age-dependent fatality. The model parameters were fitted considering the observed data from São Paulo State. Results: The partial quarantine was explained by the less virulent SARS-CoV-2 transmission, but the relaxation alone could not explain the epidemic observed in São Paulo State. However, more virulent variants plus the transmission among isolated individuals explained the increased CoViD-19 fatalities. Conclusions: The model described the CoViD-19 epidemic in São Paulo State by considering the partial quarantine, relaxation and mutations. The model provided a potential epidemiological scenario in the absence of mass vaccination.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Phases 3 Andmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Quarantine, relaxation and mutation explaining the CoViD-19 epidemic in São Paulo State (Brazil)

Hm¹,

Lpp

Ffm

et al. 2021

Preprint

Self Cite

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Deconstructing SARS‐CoV‐2 neutralization: A modular molecular framework for computational design and comparison of antibodies and nanobodies targeting the spike RBD

Tragni

Mercurio

Paoletti

et al. 2023

Journal of Medical Virology

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Since 2020 the COVID‐19 pandemic has led scientists to search for strategies to predict the transmissibility and virulence of new severe acute respiratory syndrome coronavirus 2 variants based on the estimation of the affinity of the spike receptor binding domain (RBD) for the human angiotensin‐converting enzyme 2 (ACE2) receptor and/or neutralizing antibodies. In this context, our lab developed a computational pipeline to quickly quantify the free energy of interaction at the spike RBD/ACE2 protein–protein interface, reflecting the incidence trend observed in the transmissibility/virulence of the investigated variants. In this new study, we used our pipeline to estimate the free energy of interaction between the RBD from 10 variants, and 14 antibodies (ab), or 5 nanobodies (nb), highlighting the RBD regions preferentially targeted by the investigated ab/nb. Our structural comparative analysis and interaction energy calculations allowed us to propose the most promising RBD regions to be targeted by future ab/nb to be designed by site‐directed mutagenesis of existing high‐affinity ab/nb, to increase their affinity for the target RBD region, for preventing spike‐RBD/ACE2 interactions and virus entry in host cells. Furthermore, we evaluated the ability of the investigated ab/nb to simultaneously interact with the three RBD located on the surface of the trimeric spike protein, which can alternatively be in up‐ or down‐ (all‐3‐up‐, all‐3‐down‐, 1‐up‐/2‐down‐, 2‐up‐/1‐down‐) conformations.

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Modeling SARS-CoV-2 spike/ACE2 protein–protein interactions for predicting the binding affinity of new spike variants for ACE2, and novel ACE2 structurally related human protein targets, for COVID-19 handling in the 3PM context

Tragni

Laera

et al. 2022

EPMA Journal

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Aims The rapid spread of new SARS-CoV-2 variants has highlighted the crucial role played in the infection by mutations occurring at the SARS-CoV-2 spike receptor binding domain (RBD) in the interactions with the human ACE2 receptor. In this context, it urgently needs to develop new rapid tools for quickly predicting the affinity of ACE2 for the SARS-CoV-2 spike RBD protein variants to be used with the ongoing SARS-CoV-2 genomic sequencing activities in the clinics, aiming to gain clues about the transmissibility and virulence of new variants, to prevent new outbreaks and to quickly estimate the severity of the disease in the context of the 3PM. Methods In our study, we used a computational pipeline for calculating the interaction energies at the SARS-CoV-2 spike RBD/ACE2 protein–protein interface for a selected group of characterized infectious variants of concern/interest (VoC/VoI). By using our pipeline, we built 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for the VoC B.1.1.7-United Kingdom (carrying the mutations of concern/interest N501Y, S494P, E484K at the RBD), P.1-Japan/Brazil (RBD mutations: K417T, E484K, N501Y), B.1.351-South Africa (RBD mutations: K417N, E484K, N501Y), B.1.427/B.1.429-California (RBD mutations: L452R), the B.1.141 (RBD mutations: N439K), and the recent B.1.617.1-India (RBD mutations: L452R; E484Q) and the B.1.620 (RBD mutations: S477N; E484K). Then, we used the obtained 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for predicting the interaction energies at the protein–protein interface. Results Along SARS-CoV-2 mutation database screening and mutation localization analysis, it was ascertained that the most dangerous mutations at VoC/VoI spike proteins are located mainly at three regions of the SARS-CoV-2 spike “boat-shaped” receptor binding motif, on the RBD domain. Notably, the P.1 Japan/Brazil variant present three mutations, K417T, E484K, N501Y, located along the entire receptor binding motif, which apparently determines the highest interaction energy at the SARS-CoV-2 spike RBD/ACE2 protein–protein interface, among those calculated. Conversely, it was also observed that the replacement of a single acidic/hydrophilic residue with a basic residue (E484K or N439K) at the “stern” or “bow” regions, of the boat-shaped receptor binding motif on the RBD, appears to determine an interaction energy with ACE2 receptor higher than that observed with single mutations occurring at the “hull” region or with other multiple mutants. In addition, our pipeline allowed searching for ACE2 structurally related proteins, i.e., THOP1 and NLN, which deserve to be investigated for their possible involvement in interactions with the SARS-CoV-2 spike protein, in those tissues showing a low expression of ACE2, or as a novel receptor for future spike variants. A freely available web-tool for the in silico calculation of the interaction energy at the SARS-CoV-2 spike RBD/ACE2 prot...

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Evaluating the trade-off between transmissibility and virulence of SARS-CoV-2 by mathematical modeling

Cited by 4 publications

References 11 publications

Quarantine, relaxation and mutation explaining the CoViD-19 epidemic in São Paulo State (Brazil)

Quarantine, relaxation and mutation explaining the CoViD-19 epidemic in São Paulo State (Brazil)

Deconstructing SARS‐CoV‐2 neutralization: A modular molecular framework for computational design and comparison of antibodies and nanobodies targeting the spike RBD

Modeling SARS-CoV-2 spike/ACE2 protein–protein interactions for predicting the binding affinity of new spike variants for ACE2, and novel ACE2 structurally related human protein targets, for COVID-19 handling in the 3PM context

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