Tropism of the Novel Coronavirus SARS-CoV-2 in Human Respiratory Tract: An Analysis in Ex Vivo and In Vitro Cultures

2020 ◽  
Author(s):  
Kenrie PY Hui ◽  
Man-Chun Cheung ◽  
Ranawaka APM Perera ◽  
Ka-Chun Ng ◽  
Christine BT Bui ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Ex Vivo ◽  
The Novel ◽  
Human Respiratory Tract ◽  
Novel Coronavirus

scholarly journals Status of chloroquine and hydroxychloroquine in COVID-19 infection

2020 ◽  
Vol 9 (8) ◽  
pp. 1301
Author(s):  
Savita Ramesh Shahani ◽  
Lokesh R. Shahani
Keyword(s):  
Clinical Trials ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Rna Virus ◽  
International Committee ◽  
The Novel ◽  
Human Respiratory Tract ◽  
Novel Virus ◽  
Dose Dependent

COVID-19 causing virus is a single stranded RNA virus which has spread across the globe causing human respiratory tract infection. The novel virus which started from Wuhan was named as Wuhan coronavirus or 2019 novel corona virus (2019-nCov) by the Chinese researchers. The international committee on taxonomy of viruses named the virus as SARS-CoV-2 and the disease as COVID-19. There is preliminary in vitro evidence of the ability of CQ and HCQ to inhibit SARS-CoV-2 activity. Various small group clinical studies conducted in china indicated efficacy of chloroquine and hydroxychloroquine in Covid-19 cases but results were inconclusive. Based on these studies national agencies in various countries issued guidelines mentioning that chloroquine and Hydroxychloroquine are only to be used in clinical trials or emergency use programs. However, USFDA does not recommend use of both these drugs for treatment of COVID-19 cases. Chloroquine and hydroxychloroquine are known to produce dose dependent toxicity including fatal arrhythmias therefore its possible benefit has to be assessed against its risk. Large number of international and national studies are ongoing to assess exact status of chloroquine and hydroxychloroquine for treatment and prophylaxis of COVID-19 infection. Based on these results ICMR recommend to use hydroxychloroquine for prophylaxis of COVID-19 in India and hydroxychloroquine has been is included  in schedule H1 hence they can be sold by pharmaceutical chemists only strictly with a valid prescription and require record to be maintained but chloroquine is still under schedule H which require to be sold with prescription. 

scholarly journals Tropism and innate host responses of influenza A/H5N6 virus: an analysis ofex vivoandin vitrocultures of the human respiratory tract

2017 ◽  
Vol 49 (3) ◽  
pp. 1601710 ◽  
Author(s):  
Kenrie P. Y. Hui ◽  
Louisa L. Y. Chan ◽  
Denise I. T. Kuok ◽  
Chris K. P. Mok ◽  
Zi-feng Yang ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Influenza A ◽  
H5n1 Virus ◽  
Ex Vivo ◽  
Alveolar Epithelial Cells ◽  
Human Respiratory Tract ◽  
Human Bronchus ◽  
Cytokines And Chemokines ◽  
Hpai H5n1

Since their first isolation in 2013, influenza A/H5N6 viruses have spread amongst poultry across multiple provinces in China and to Laos, Vietnam and Myanmar. So far, there have been 14 human H5N6 infections with 10 fatalities.We investigated the tropism, replication competence and cytokine induction of one human and two avian H5N6 isolates inex vivoandin vitrocultures derived from the human respiratory tract. Virus tropism and replication were studied inex vivocultures of human nasopharynx, bronchus and lung. Induction of cytokines and chemokines was measuredin vitroin virus-infected primary human alveolar epithelial cells.Human H5N6 virus replicated more efficiently than highly pathogenic avian influenza (HPAI) H5N1 virus and as efficiently as H1N1pdm inex vivohuman bronchus and lung and was also able to replicate inex vivocultures of human nasopharynx. Avian H5N6 viruses replicated less efficiently than H1N1pdm in human bronchial tissues and to similar titres as HPAI H5N1 in the lung. While the human H5N6 virus had affinity for avian-like receptors, the two avian isolates had binding affinity for both avian- and human-like receptors. All three H5N6 viruses were less potent inducers of pro-inflammatory cytokines compared with H5N1 virus.Human H5N6 virus appears better adapted to infect the human airways than H5N1 virus and may pose a significant public health threat.

scholarly journals Risk Assessment of the Tropism and Pathogenesis of the Highly Pathogenic Avian Influenza A/H7N9 Virus Using Ex Vivo and In Vitro Cultures of Human Respiratory Tract

2019 ◽  
Vol 220 (4) ◽  
pp. 578-588 ◽  
Author(s):  
Louisa L Y Chan ◽  
Kenrie P Y Hui ◽  
Denise I T Kuok ◽  
Christine H T Bui ◽  
Ka-chun Ng ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Respiratory Tract ◽  
Highly Pathogenic Avian Influenza ◽  
Ex Vivo ◽  
Alveolar Epithelial Cells ◽  
H7n9 Virus ◽  
Human Respiratory Tract ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza

Abstract Background Highly pathogenic avian influenza (HPAI)-H7N9 virus arising from low pathogenic avian influenza (LPAI)-H7N9 virus with polybasic amino acid substitutions in the hemagglutinin was detected in 2017. Methods We compared the tropism, replication competence, and cytokine induction of HPAI-H7N9, LPAI-H7N9, and HPAI-H5N1 in ex vivo human respiratory tract explants, in vitro culture of human alveolar epithelial cells (AECs) and pulmonary microvascular endothelial cells (HMVEC-L). Results Replication competence of HPAI- and LPAI-H7N9 were comparable in ex vivo cultures of bronchus and lung. HPAI-H7N9 predominantly infected AECs, whereas limited infection was observed in bronchus. The reduced tropism of HPAI-H7N9 in bronchial epithelium may explain the lack of human-to-human transmission despite a number of mammalian adaptation markers. Apical and basolateral release of virus was observed only in HPAI-H7N9- and H5N1-infected AECs regardless of infection route. HPAI-H7N9, but not LPAI-H7N9 efficiently replicated in HMVEC-L. Conclusions Our findings demonstrate that a HPAI-H7N9 virus efficiently replicating in ex vivo cultures of human bronchus and lung. The HPAI-H7N9 was more efficient at replicating in human AECs and HMVEC-L than LPAI-H7N9 implying that endothelial tropism may involve in pathogenesis of HPAI-H7N9 disease.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

scholarly journals Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

scholarly journals Characterization of the SARS-CoV-2 coronavirus X4-like accessory protein

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Nkwachukwu Oziamara Okoro ◽  
Arome Solomon Odiba
Keyword(s):  
Rapid Development ◽  
Protein A ◽  
The Novel ◽  
Quality Model ◽  
A Value ◽  
Model Protein ◽  
Novel Coronavirus ◽  
Global Threat

Abstract Background The novel coronavirus SARS-CoV-2 is currently a global threat to health and economies. Therapeutics and vaccines are in rapid development; however, none of these therapeutics are considered as absolute cure, and the potential to mutate makes it necessary to find therapeutics that target a highly conserved regions of the viral structure. Results In this study, we characterized an essential but poorly understood coronavirus accessory X4 protein, a core and stable component of the SARS-CoV family. Sequence analysis shows a conserved ~ 90% identity between the SARS-CoV-2 and previously characterized X4 protein in the database. QMEAN Z score of the model protein shows a value of around 0.5, within the acceptable range 0–1. A MolProbity score of 2.96 was obtained for the model protein and indicates a good quality model. The model has Ramachandran values of φ = − 57o and ψ = − 47o for α-helices and values of φ = − 130o and ψ = + 140o for twisted sheets. Conclusions The protein data obtained from this study provides robust information for further in vitro and in vivo experiment, targeted at devising therapeutics against the virus. Phylogenetic analysis further supports previous evidence that the SARS-CoV-2 is positioned with the SL-CoVZC45, BtRs-BetaCoV/YN2018B and the RS4231 Bat SARS-like corona viruses.

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