Abstract
In December 2019, an atypical pneumonia invaded the city of Wuhan, China, and the causative agent of this disease turned out to be a new coronavirus. In January 2020, the World Health Organization named the new coronavirus 2019-nCoV and subsequently it is referred to as SARS-CoV2 and the related disease as CoViD-19 [9]. Very quickly, the epidemic led to a pandemic and it is now a worldwide emergency requiring the creation of new antiviral therapies and a related vaccine. The purpose of this article is to review and investigate further the molecular mechanism by which the SARS-CoV2 virus infection proceeds via the formation of a hetero-trimer between its protein S, the ACE2 receptor and the B0AT1 protein, which is the “entry receptor” for the infection process involving membrane fusion [10]. A reverse engineering process uses the formalism of the Hill function to represent the functions related to the dynamics of the biochemical interactions of the viral infection process. Then, using a logical evaluation of viral density that measures the rate at which the cells are hijacked by the virus (and they provide a place for the virus to replicate) and considering the “time delay” given by the interaction between cell and virus, the expected duration of the incubation period is predicted. The conclusion is that the density of the virus varies from the “exposure time” to the “interaction time” (virus-cells). This model can be used both to evaluate the infectious condition and to analyze the incubation period.
Background
The ongoing threat of the new coronavirus SARS-CoV2 pandemic is alarming and strategies for combating infection are highly desired. This RNA virus belongs to the β-coronavirus genus and is similar in some features to SARS-CoV. Currently, no vaccine or approved medical treatment is available. The complex dynamics of the rapid spread of this virus can be demonstrated with the aid of a computational framework.
Methods
A mathematical model based on the principles of cell-virus interaction is developed in this manuscript. The amino acid sequence of S proein and its interaction with the ACE-2 protein is mimicked with the aid of Hill function. The mathematical model with delay is solved with the aid of numerical solvers and the parametric values are obtained with the help of MCMC algorithm.
Results
A delay differential equation model is developed to demonstrate the dynamics of target cells, infected cells and the SARS-CoV2. The important parameters and coefficients are demonstrated with the aid of numerical computations. The resulting thresholds and forecasting may prove to be useful tools for future experimental studies and control strategies.
Conclusions
From the analysis, I is concluded that control strategy via delay is a promising technique and the role of Hill function formalism in control strategies can be better interpreted in an inexpensive manner with the aid of a theoretical framework.
[1]
M. Sansom,et al.
Computational virology: From the inside out
,
2016,
Biochimica et biophysica acta.
[2]
G. Herrler,et al.
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
,
2020,
Cell.
[3]
Chengsheng Zhang,et al.
Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2
,
2005,
The EMBO journal.
[4]
Lubna Sherin,et al.
Cancer drug therapy and stochastic modeling of “nano-motors”
,
2018,
International journal of nanomedicine.
[5]
B. Graham,et al.
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
,
2020,
Science.
[6]
W. Ko,et al.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges
,
2020,
International Journal of Antimicrobial Agents.
[7]
D. Cummings,et al.
Hospital outbreak of Middle East respiratory syndrome coronavirus.
,
2013,
The New England journal of medicine.
[8]
A. Walls,et al.
Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion
,
2019,
Cell.
[9]
G. Air,et al.
Quantitative Comparison of Human Parainfluenza Virus Hemagglutinin-Neuraminidase Receptor Binding and Receptor Cleavage
,
2013,
Journal of Virology.
[10]
E. Holmes,et al.
A new coronavirus associated with human respiratory disease in China
,
2020,
Nature.
[11]
Choujun Zhan,et al.
Parameter estimation in systems biology models using spline approximation
,
2011,
BMC Systems Biology.
[12]
G. Brooks,et al.
Interaction of the Coronavirus Nucleoprotein with Nucleolar Antigens and the Host Cell
,
2002,
Journal of Virology.
[13]
Don Klinkenberg,et al.
Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020
,
2020,
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.
[14]
Ayesha Sohail,et al.
AI- modelling of molecular identification and feminization of wolbachia infected Aedes aegypti.
,
2019,
Progress in biophysics and molecular biology.
[15]
B. Canard,et al.
The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade
,
2020,
Antiviral Research.
[16]
John L. Sullivan,et al.
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
,
2003,
Nature.
[17]
Christian Drosten,et al.
Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response
,
2011,
Journal of Virology.
[18]
Frank Grosveld,et al.
A human monoclonal antibody blocking SARS-CoV-2 infection
,
2020,
Nature Communications.