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1.
PLoS Pathog ; 17(4): e1009149, 2021 04.
Article in English | MEDLINE | ID: covidwho-1194504

ABSTRACT

The COVID-19 pandemic has demonstrated the serious potential for novel zoonotic coronaviruses to emerge and cause major outbreaks. The immediate animal origin of the causative virus, SARS-CoV-2, remains unknown, a notoriously challenging task for emerging disease investigations. Coevolution with hosts leads to specific evolutionary signatures within viral genomes that can inform likely animal origins. We obtained a set of 650 spike protein and 511 whole genome nucleotide sequences from 222 and 185 viruses belonging to the family Coronaviridae, respectively. We then trained random forest models independently on genome composition biases of spike protein and whole genome sequences, including dinucleotide and codon usage biases in order to predict animal host (of nine possible categories, including human). In hold-one-out cross-validation, predictive accuracy on unseen coronaviruses consistently reached ~73%, indicating evolutionary signal in spike proteins to be just as informative as whole genome sequences. However, different composition biases were informative in each case. Applying optimised random forest models to classify human sequences of MERS-CoV and SARS-CoV revealed evolutionary signatures consistent with their recognised intermediate hosts (camelids, carnivores), while human sequences of SARS-CoV-2 were predicted as having bat hosts (suborder Yinpterochiroptera), supporting bats as the suspected origins of the current pandemic. In addition to phylogeny, variation in genome composition can act as an informative approach to predict emerging virus traits as soon as sequences are available. More widely, this work demonstrates the potential in combining genetic resources with machine learning algorithms to address long-standing challenges in emerging infectious diseases.


Subject(s)
Biological Evolution , Coronaviridae Infections/diagnosis , Coronaviridae Infections/virology , Coronaviridae/pathogenicity , Genome, Viral , Machine Learning , Spike Glycoprotein, Coronavirus/metabolism , Animals , Coronaviridae Infections/genetics , Coronaviridae Infections/metabolism , Phylogeny , Spike Glycoprotein, Coronavirus/genetics
2.
Front Pharmacol ; 12: 634176, 2021.
Article in English | MEDLINE | ID: covidwho-1150704

ABSTRACT

The outbreak of SARS-CoV-2 virus caused more than 80,155,187 confirmed COVID-19 cases worldwide, which has posed a serious threat to global public health and the economy. The development of vaccines and discovery of novel drugs for COVID-19 are urgently needed. Although the FDA-approved SARS-CoV-2 vaccines has been launched in many countries recently, the strength of safety, stringent storage condition and the possibly short-term immunized efficacy remain as the major challenges in the popularity and recognition of using vaccines against SARS-CoV-2. With the spike-receptor binding domain (RBD) of SARS-CoV-2 being responsible for binding to human angiotensin-converting enzyme 2 receptor (hACE2), ACE2 is identified as the receptor for the entry and viral infection of SARS-CoV-2. In this study, molecular docking and biolayer interferometry (BLI) binding assay were adopted to determine the direct molecular interactions between natural small-molecule, 1,2,3,4,6-Pentagalloyl glucose (PGG) and the spike-RBD of the SARS-CoV-2. Our results showed that PGG preferentially binds to a pocket that contains residues Glu 340 to Lys 356 of spike-RBD with a relatively low binding energy of -8 kcal/mol. BLI assay further confirmed that PGG exhibits a relatively strong binding affinity to SARS-CoV-2-RBD protein in comparison to hACE2. In addition, both ELISA and immunocytochemistry assay proved that PGG blocks SARS-CoV-2-RBD binding to hACE2 dose dependently in cellular level. Notably, PGG was confirmed to abolish the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of wild type SARS-CoV-2 virus in human host cells. Finally, maximal tolerated dose (MTD) studies revealed that up to 200 mg/kg/day of PGG was confirmed orally safe in mice. Our findings suggest that PGG may be a safe and potential antiviral agent against the COVID-19 by blockade the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. Therefore, PGG may be considered as a safe and natural antiviral agent for its possible preventive application in daily anti-virus hygienic products such as a disinfectant spray or face mask.

3.
Int J Nanomedicine ; 16: 383-402, 2021.
Article in English | MEDLINE | ID: covidwho-1076350

ABSTRACT

Advancements in analytical diagnostic systems for point-of-care (POC) application have gained considerable attention because of their rapid operation at the site required to manage severe diseases, even in a personalized manner. The POC diagnostic devices offer easy operation, fast analytical outcome, and affordable cost, which promote their advanced research and versatile adoptability. Keeping advantages in view, considerable efforts are being made to design and develop smart sensing components such as miniaturized transduction, interdigitated electrodes-based sensing chips, selective detection at low level, portable packaging, and sustainable durability to promote POC diagnostics according to the needs of patient care. Such effective diagnostics systems are in demand, which creates the challenge to make them more efficient in every aspect to generate a desired bio-informatic needed for better health access and management. Keeping advantages and scope in view, this mini review focuses on practical scenarios associated with miniaturized analytical diagnostic devices at POC application for targeted disease diagnostics smartly and efficiently. Moreover, advancements in technologies, such as smartphone-based operation, paper-based sensing assays, and lab-on-a-chip (LOC) which made POC more sensitive, informative, and suitable for major infectious disease diagnosis, are the main focus here. Besides, POC diagnostics based on automated patient sample integration with a sensing platform is continuously improving therapeutics interventions against specific infectious disease. This review also discussed challenges associated with state-of-the-art technology along with future research opportunities to design and develop next generation POC diagnostic systems needed to manage infectious diseases in a personalized manner.


Subject(s)
Point-of-Care Testing , Precision Medicine/methods , Communicable Diseases/diagnosis , Humans , Lab-On-A-Chip Devices , Smartphone
4.
Am J Trop Med Hyg ; 103(2): 597-602, 2020 08.
Article in English | MEDLINE | ID: covidwho-610554

ABSTRACT

As of June 11, 2020, the Democratic Republic of the Congo (DRC) has reported 4,258 COVID-19 cases with 90 deaths. With other African countries, the DRC faces the challenge of striking a balance between easing public health lockdown measures to curtail the spread of SARS-CoV-2 and minimizing both economic hardships for large sectors of the population and negative impacts on health services for other infectious and noninfectious diseases. The DRC recently controlled its tenth Ebola virus disease (EVD) outbreak, but COVID-19 and a new EVD outbreak beginning on June 1, 2020 in the northwest Équateur Province have added an additional burden to health services. Although the epidemiology and transmission of EVD and COVID-19 differ, leveraging the public health infrastructures and experiences from coordinating the EVD response to guide the public health response to COVID-19 is critical. Building on the DRC's 40 years of experience with 10 previous EVD outbreaks, we highlight the DRC's multi-sectoral public health approach to COVID-19, which includes community-based screening, testing, contact-tracing, risk communication, community engagement, and case management. We also highlight remaining challenges and discuss the way forward for achieving control of both COVID-19 and EVD in the DRC.


Subject(s)
Coronavirus Infections/epidemiology , Delivery of Health Care/organization & administration , Hemorrhagic Fever, Ebola/epidemiology , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , Case Management , Contact Tracing , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Democratic Republic of the Congo/epidemiology , Health Communication , Hemorrhagic Fever, Ebola/diagnosis , Hemorrhagic Fever, Ebola/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , SARS-CoV-2
5.
MMWR Morb Mortal Wkly Rep ; 69(19): 594-598, 2020 May 15.
Article in English | MEDLINE | ID: covidwho-209116

ABSTRACT

Correctional and detention facilities face unique challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1-3). Among >10 million annual admissions to U.S. jails, approximately 55% of detainees are released back into their communities each week (4); in addition, staff members at correctional and detention facilities are members of their local communities. Thus, high rates of COVID-19 in correctional and detention facilities also have the potential to influence broader community transmission. In March 2020, the Louisiana Department of Health (LDH) began implementing surveillance for COVID-19 among correctional and detention facilities in Louisiana and identified cases and outbreaks in many facilities. In response, LDH and CDC developed and deployed the COVID-19 Management Assessment and Response (CMAR) tool to guide technical assistance focused on infection prevention and control policies and case management with correctional and detention facilities. This report describes COVID-19 prevalence in correctional and detention facilities detected through surveillance and findings of the CMAR assessment. During March 25-April 22, 489 laboratory-confirmed COVID-19 cases, including 37 (7.6%) hospitalizations and 10 (2.0%) deaths among incarcerated or detained persons, and 253 cases, including 19 (7.5%) hospitalizations and four (1.6%) deaths among staff members were reported. During April 8-22, CMAR telephone-based assessments were conducted with 13 of 31 (42%) facilities with laboratory-confirmed cases and 11 of 113 (10%) facilities without known cases. Administrators had awareness and overall understanding of CDC guidance for prevention of transmission in these facilities but reported challenges in implementation, related to limited space to quarantine close contacts of COVID-19 patients and inability of incarcerated and detained persons to engage in social distancing, particularly in dormitory-style housing. CMAR was a useful tool that helped state and federal public health officials assist multiple correctional and detention facilities to better manage COVID-19 patients and guide control activities to prevent or mitigate transmission.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Prisons , Public Health Practice , COVID-19 , Female , Humans , Louisiana/epidemiology , Male
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