Modelling SARS-CoV-2 Dynamics: Implications for Therapy

@article{Kim2020ModellingSD,
  title={Modelling SARS-CoV-2 Dynamics: Implications for Therapy},
  author={Kwang Su Kim and Keisuke Ejima and Yusuke Ito and Shoya Iwanami and Hirofumi Ohashi and Yoshiki Koizumi and Yusuke Asai and Shinji Nakaoka and Koichi Watashi and Robin N. Thompson and Shingo Iwami},
  journal={medRxiv},
  year={2020}
}
The scientific community is focussed on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data collected from the same specimen (throat / nasal swabs or nasopharyngeal / sputum / tracheal aspirate), we compare within-host dynamics for patients infected in the… Expand
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References

SHOWING 1-10 OF 29 REFERENCES
A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus—A possible reference for coronavirus disease‐19 treatment option
TLDR
The literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, is discussed, so that the potential for the use ofLPV in patientswith COVID‐19 is clarified. Expand
Modelling Ebola virus dynamics: Implications for therapy.
TLDR
A novel mathematical model is developed to quantitatively analyse human viral load data obtained during the 2000/01 Uganda EBOV outbreak and it is found that nucleoside analogue- and siRNA-based therapies are effective if a therapy with a >50% inhibition rate is initiated within a few days post-symptom-onset. Expand
Severe acute respiratory syndrome.
TLDR
The concerted and coordinated response that contained SARS is a triumph for global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats. Expand
Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study
TLDR
The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage. Expand
Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia
TLDR
There is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019 and considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Expand
A Novel Coronavirus from Patients with Pneumonia in China, 2019
TLDR
Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans. Expand
Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody
TLDR
It is reported for the first time that a SARS-CoV-specific human monoclonal antibody,CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM), suggesting that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019- nCoV infections. Expand
Detection of SARS Coronavirus in Patients with Severe Acute Respiratory Syndrome by Conventional and Real-Time Quantitative Reverse Transcription-PCR Assays
TLDR
The quantitative real-time RT-PCR assay for SARS CoV is potentially useful for early detection and suggests that genomic RNA is the predominant viral RNA species in clinical samples. Expand
Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations
TLDR
The importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak of pneumonia will not become a global pandemic, is emphasised. Expand
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
TLDR
This study evaluated the antiviral efficiency of five FAD-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine and two well-known broad-spectrum antiviral drugs remdesivir and favipiravir against a clinical isolate of 2019-nCoV in vitro. Expand
...
1
2
3
...