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1.
Viruses ; 14(3)2022 03 13.
Article in English | MEDLINE | ID: covidwho-1742726

ABSTRACT

The prolonged duration of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has resulted in the continuous emergence of variants of concern (VOC, e.g., Omicron) and variants of interest (VOI, e.g., Lambda). These variants have challenged the protective efficacy of current COVID-19 vaccines, thus calling for the development of novel therapeutics against SARS-CoV-2 and its VOCs. Here, we constructed a novel fusion inhibitor-based recombinant protein, denoted as 5-Helix, consisting of three heptad repeat 1 (HR1) and two heptad repeat 2 (HR2) fragments. The 5-Helix interacted with the HR2 domain of the viral S2 subunit, the most conserved region in spike (S) protein, to block homologous six-helix bundle (6-HB) formation between viral HR1 and HR2 domains and, hence, viral S-mediated cell-cell fusion. The 5-Helix potently inhibited infection by pseudotyped SARS-CoV-2 and its VOCs, including Delta and Omicron variants. The 5-Helix also inhibited infection by authentic SARS-CoV-2 wild-type (nCoV-SH01) strain and its Delta variant. Collectively, our findings suggest that 5-Helix can be further developed as either a therapeutic or prophylactic to treat and prevent infection by SARS-CoV-2 and its variants.


Subject(s)
COVID-19 , Viral Envelope Proteins , COVID-19 Vaccines , Humans , Membrane Glycoproteins/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/metabolism
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323696

ABSTRACT

Epidemic models play a key role in understanding and responding to the emerging COVID-19 pandemic. Widely used compartmental models are static and are of limited use to evaluate intervention strategies with the emerging pandemic. Applying the technology of data assimilation, we propose a Bayesian updating approach for estimating epidemiological parameters using observable information for the purpose of assessing the impacts of different intervention strategies. We adopt a concise renewal model and propose new parameters by disentangling the reduction of instantaneous reproduction number Rt into mitigation and suppression factors for quantifying intervention impacts at a finer granularity. Then we developed a data assimilation framework for estimating these parameters including constructing an observation function and developing a Bayesian updating scheme. A statistical analysis framework is then built to quantify the impact of intervention strategies by monitoring the evolution of these estimated parameters. By Investigating the impacts of intervention measures of European countries, the United States and Wuhan with the framework, we reveal the effects of interventions in these countries and the resurgence risk in the USA.

3.
Signal Transduct Target Ther ; 5(1): 220, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-1387194
4.
Adv Exp Med Biol ; 1318: 435-448, 2021.
Article in English | MEDLINE | ID: covidwho-1222728

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2, the disease has spread rapidly worldwide and developed into a global pandemic, causing a significant impact on the global health system and economic development. Scientists have been racing to find effective drugs and vaccines for the treatment and prevention of COVID-19. However, due to the diversity of clinical manifestations caused by COVID-19, no standard antiviral regimen beyond supportive therapy has been established. Ongoing clinical trials are underway to evaluate the efficacy of drugs that primarily act on the viral replication cycle or enhanced immunity of patients. This chapter will summarize the currently used antiviral and adjuvant therapies in clinical practice and provide a theoretical basis for the future treatment of COVID-19.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , COVID-19 Vaccines , Humans , Pandemics , SARS-CoV-2
5.
Yue Dan Yi Shi Fa Bao Gao = Angle Health Law Review ; - (54):49-59, 2021.
Article in Chinese | ProQuest Central | ID: covidwho-1204297

ABSTRACT

It is a great shock to the legal system by COVID-19 or the spread of so-called severe acute respiratory syndrome coronavirus, which made it hard to react. Even though there might be some general principles for emergency in the Administrative Law, they belong to individual administrative cases. Moreover, the regulation for emergency in Constitution depends on the political decision of the decision-maker. Therefore, it is necessary to give the administrative agencies the possibility for the discretion in the field of the general theory of Administrative Law and of Public Health concerning to emergency due to the pandemic. The review of the norm-interpretating should be loose as well. Meanwhile, in order to avoid abusing rights, an regular examination on its validity and rationality should also be performed. Besides, administrative discretion should be made from the consensus decision by specialists.

6.
Adv Ther (Weinh) ; : 2000224, 2021 Feb 22.
Article in English | MEDLINE | ID: covidwho-1095226

ABSTRACT

SARS-CoV-2 caused the emerging epidemic of coronavirus disease in 2019 (COVID-19). To date, there are more than 82.9 million confirmed cases worldwide, there is no clinically effective drug against SARS-CoV-2 infection. The conserved properties of the membrane fusion domain of the spike (S) protein across SARS-CoV-2 make it a promising target to develop pan-CoV therapeutics. Herein, two clinically approved drugs, Itraconazole (ITZ) and Estradiol benzoate (EB), are found to inhibit viral entry by targeting the six-helix (6-HB) fusion core of SARS-CoV-2 S protein. Further studies shed light on the mechanism that ITZ and EB can interact with the heptad repeat 1 (HR1) region of the spike protein, to present anti-SARS-CoV-2 infections in vitro, indicating they are novel potential therapeutic remedies for COVID-19 treatment. Furthermore, ITZ shows broad-spectrum activity targeting 6-HB in the S2 subunit of SARS-CoV and MERS-CoV S protein, inspiring that ITZ have the potential for development as a pan-coronavirus fusion inhibitor.

7.
Transp Res E Logist Transp Rev ; 146: 102214, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1039579

ABSTRACT

Covid-19, the global pandemic, has taught us the importance of contactless delivery service and robotic automation. Using self-driving delivery robots can provide flexibility for on-time deliveries and help better protect both driver and customers by minimizing contact. To this end, this paper introduces a new vehicle routing problem with time windows and delivery robots (VRPTWDR). With the help of delivery robots, considerable operational time savings can be achieved by dispatching robots to serve nearby customers while a driver is also serving a customer. We provide a mathematical model for the VRPTWDR and investigate the challenges and benefits of using delivery robots as assistants for city logistics. A two-stage matheurisitic algorithm is developed to solve medium scale VRPTWDR instances. Finally, results of computational experiments demonstrate the value of self-driving delivery robots in urban areas by highlighting operational limitations on route planning.

8.
Int J Hosp Manag ; 92: 102760, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-927774

ABSTRACT

This study investigates how peer-to-peer accommodation (P2PA) hosts in China have responded to the COVID-19 pandemic. A multi-case study approach was adopted to depict the decision-making logic of three different types of hosts-speculators, diplomats, and entrepreneurs-based on an awareness-motivation-capability (AMC) framework under COVID-19. The findings highlight the role of owner motivation (profit/sharing/entrepreneurial-driven) and capabilities, such as having a unique value proposition and linkages with other hospitality experience, under COVID-19. Meanwhile, the platform collaboration capability failed to support survival during the pandemic. Moreover, the current study indicated that, after the COVID-19, entrepreneurs will continue to innovate, diplomats' operations will remain unchanged and speculators will quit hosting. Hence, COVID-19 is an accelerator of P2P industry that reserving the hosts who embrace the original features of the P2PA sector, e.g. sharing and a focus on the experience, and eliminating the hosts who have diluted the uniqueness of the sector.

9.
Ieee Computational Intelligence Magazine ; 15(4):23-33, 2020.
Article in English | Web of Science | ID: covidwho-900842

ABSTRACT

Epidemic models play a key role in understanding and responding to the emerging COVID-19 pandemic. Widely used compartmental models are static and are of limited use to evaluate intervention strategies of combatting the pandemic. Applying the technology of data assimilation, we propose a Bayesian updating approach for estimating epidemiological parameters using observable information to assess the impacts of different intervention strategies. We adopt a concise renewal model and propose new parameters by disentangling the reduction of instantaneous reproduction number Rt into mitigation and suppression factors to quantify intervention impacts at a finer granularity. A data assimilation framework is developed to estimate these parameters including constructing an observation function and developing a Bayesian updating scheme. A statistical analysis framework is built to quantify the impacts of intervention strategies by monitoring the evolution of the estimated parameters. We reveal the intervention impacts in European countries and Wuhan and the resurgence risk in the United States.

10.
Acta Pharmacol Sin ; 41(9): 1141-1149, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-694139

ABSTRACT

Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. In this review, we highlight recent research advance in the structure, function and development of antivirus drugs targeting the S protein.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Spike Glycoprotein, Coronavirus/physiology , Virus Internalization/drug effects , Betacoronavirus/drug effects , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Drug Discovery/methods , Humans , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , SARS-CoV-2
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