scholarly journals The correlation between antiviral drug, immune response and HIV viral load

2020 ◽  
Author(s):  
Mesfin Asfaw Taye

Developing antiviral drugs is an exigent task since viruses mutate to overcome the effect of antiviral drugs. As a result, the efficacy of most antiviral drugs is short-lived. To include this effect, we modify the Neumann and Dahari model. Considering the fact that the efficacy of the antiviral drug varies in time, the differential equations introduced in the previous model systems are rewritten to study the correlation between the viral load and antiviral drug. The effect of antiviral drug that either prevents infection or stops the production of a virus is explored. First, the efficacy of the drug is considered to decreases monotonously as time progresses. In this case, our result depicts that when the efficacy of the drug is low, the viral load decreases and increases back in time revealing the effect of the antiviral drugs is short-lived. On the other hand, for the antiviral drug with high efficacy, the viral load as well as the number of infected cells monotonously decreases while the number of uninfected cells increases. The dependence of the critical drug efficacy on time is also explored. Moreover, the correlation between viral load, the antiviral drug, and CTL response is also explored. In this case, not only the dependence for the basic reproduction ratio on the model parameters is explored but also we analyze the critical drug efficacy as a function of time. We show that the term related to the basic reproduction ratio increases when the CTL response step up. A simple analytically solvable mathematical model is also presented to analyze the correlation between viral load and antiviral drugs.PACS numbersValid PACS appear here

2020 ◽  
Author(s):  
Prashant Dogra ◽  
Javier Ruiz-Ramírez ◽  
Kavya Sinha ◽  
Joseph D. Butner ◽  
Maria J Peláez ◽  
...  

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogen of immense public health concern. Efforts to control the disease have only proven mildly successful, and the disease will likely continue to cause excessive fatalities until effective preventative measures (such as a vaccine) are developed. To develop disease management strategies, a better understanding of SARS-CoV-2 pathogenesis and population susceptibility to infection are needed. To this end, physiologically-relevant mathematical modeling can provide a robust in silico tool to understand COVID-19 pathophysiology and the in vivo dynamics of SARS-CoV-2. Guided by ACE2-tropism (ACE2 receptor dependency for infection) of the virus, and by incorporating cellular-scale viral dynamics and innate and adaptive immune responses, we have developed a multiscale mechanistic model for simulating the time-dependent evolution of viral load distribution in susceptible organs of the body (respiratory tract, gut, liver, spleen, heart, kidneys, and brain). Following calibration with in vivo and clinical data, we used the model to simulate viral load progression in a virtual patient with varying degrees of compromised immune status. Further, we conducted global sensitivity analysis of model parameters and ranked them for their significance in governing clearance of viral load to understand the effects of physiological factors and underlying conditions on viral load dynamics. Antiviral drug therapy, interferon therapy, and their combination was simulated to study the effects on viral load kinetics of SARS-CoV-2. The model revealed the dominant role of innate immunity (specifically interferons and resident macrophages) in controlling viral load, and the impotance of timing when initiating therapy following infection.Graphical Abstract


Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Manish Kumar ◽  
Chandra Prakash Jain

Background: An outbreak of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection or COVID 19, causing serious threats to all around the world. Until an effective and safe vaccine for novel coronavirus is developed by scientists, current drug therapy should by optimize for the control and treatment of COVID 19. Objective: In this manuscript, we are presenting a perspective on possible benefits of reformulating antiviral drug dosage form with nanoemulsion system against novel coronavirus infection. Methods: Literature review has been done on COVID 19, treatment strategies, novel drug delivery systems and role of pulmonary surfactant on lungs protection. Results: Nanoemulsion system and its components have certain biophysical properties which could increase the efficacy of drug therapy. Antiviral drugs, delivered through a nanoemulsion system containing P-gp inhibitor (surfactant and cosolvent), can inhibit the cellular resistance to drugs and would potentiate the antiviral action of drugs. Pulmonary surfactant (PS) assisted antiviral drug delivery by nanoemulsion system could be another effective approach for the treatment of COVID 19. Use of functional excipients like pulmonary surfactant (PS) and surfactant proteins (SPs), in the formulation of the antiviral drug-loaded nanoemulsion system can improve the treatment of coronavirus infection. Conclusion: In our opinion for synergizing antiviral action, lipid and protein portion of PS and their commercial analogs should be explored by pharmaceutical scientists to use them as a functional excipient in the formulation of antiviral drugloaded nanoemulsion system.


2020 ◽  
Vol 39 (15) ◽  
pp. 2051-2066 ◽  
Author(s):  
Rui Wang ◽  
Ante Bing ◽  
Cathy Wang ◽  
Yuchen Hu ◽  
Ronald J. Bosch ◽  
...  

2021 ◽  
Vol 56 (5) ◽  
pp. 606-614
Author(s):  
Seth C. Kalichman ◽  
Moira O. Kalichman ◽  
Ellen Banas ◽  
Marnie Hill ◽  
Harold Katner

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