Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 56
Filter
1.
Rhode Island Medical Journal ; 105(3):24-27, 2022.
Article in English | ProQuest Central | ID: covidwho-1781825

ABSTRACT

Expanding addiction treatment services in Rhode Island has never been more urgent. Today, we face colliding syndemics of COVID-19, preventable drug overdoses, and HIV, with another year of record overdoses. While the treatment of substance use disorder (SUD) is an sential of general medical care, numerous barriers prevent broader treatment access for patients in Rhode Island. Buprenorphine and methadone therapy have restrictions that are not applied to other areas in medicine, including for more dangerous medications. In this piece, we highlight existing barriers to care, applaud current progress being made in our state, and provide recommendations for next steps to turn the tide of this deadly epidemic. We hope that these proposed changes will help develop a robust treatment landscape for all patients with SUD in Rhode Island.

2.
Vaccine ; 40(19): 2696-2704, 2022 Apr 26.
Article in English | MEDLINE | ID: covidwho-1764022

ABSTRACT

OBJECTIVES: Little is known about how the coronavirus disease 2019 (COVID-19) pandemic affected influenza vaccine utilization and disparities. We sought to estimate changes in the likelihood of receiving an influenza vaccine across different demographic subgroups during the COVID-19 pandemic. METHODS: In this cohort study, we analyzed influenza vaccine uptake from 2019 to 2020 using Optum commercial insurance claims data. Eligible individuals were aged 18 or above in 2018 and continuously enrolled from 08/01/2018 through 12/31/2020. Multivariable logistic regressions were fitted for the individual-level influenza vaccine uptake. Adjusting for demographic factors and medical histories, we estimated probabilities of receiving influenza vaccines before and after the COVID-19 pandemic across demographic subgroups. RESULTS: From August to December 2019, unadjusted influenza vaccination rate was 42.3%, while in the same period of 2020, the vaccination rate increased to 45.9%. Females had a higher vaccination rate in 2019 (OR: 1.16, 95% CI 1.15-1.16), but the increase was larger for males. Blacks and Hispanics had lower vaccination rates relative to whites in both flu seasons. Hispanics showed a greater increase in vaccination rate, increasing by 7.8 percentage points (p < .001) compared to 4.4 (p < .001) for whites. The vaccination rate for Blacks increased by 5.2 percentage points (p < .001). All income groups experienced vaccination improvements, but poorer individuals had lower vaccination rates in both seasons. The most profound disparities occurred when educational cohort were considered. The vaccination rate increased among college-educated enrollees by 8.8 percentage points (p < .001) during the pandemic compared to an increase of 2.8 percentage points (p < .001) for enrollees with less than a 12th grade education. Past influenza infections or vaccination increased the likelihood of vaccination (p < .001). CONCLUSIONS: The COVID-19 pandemic was associated with increased influenza vaccine utilization. Disparities persisted but narrowed with respect to gender and race but worsened with respect to income and educational attainment.

3.
Open Forum Infectious Diseases ; 8(SUPPL 1):S511, 2021.
Article in English | EMBASE | ID: covidwho-1746366

ABSTRACT

Background. Throughout the SARS-CoV-2 pandemic, there have been many questions about how COVID-19 affects patients living with HIV (PLWH). We examined the clinical courses of 45 PLWH who required hospitalization with SARS-CoV-2 infection. Methods. This is a retrospective cohort study in which ICD-10 codes were used to identify PLWH who were admitted to three large hospital systems in Memphis, TN with COVID-19. We included all patients ≥ 18 years of age with HIV and a documented positive SARS-CoV-2 PCR test. After manual ion from the electronic health records, chi-squared and T-tests were performed to evaluate associations between patient-level factors and outcomes. Results. A total of 45 patients with HIV who tested positive for SARS-CoV-2 were admitted to Memphis, TN area hospitals between March 2020 and October 2020. 18 (40%) were female, 43 (95.6%) were Black, and the average age was 50.3 years (SD 12.6). The average BMI was 30.2 (SD 8.6). 40 (88.9%) patients admitted had at least one comorbidity with the most common being hypertension (28 patients, 62.2%) and diabetes (14 patients, 31.1%). 24 (46.7%) patients had a Charlson Comorbidity Index > 3. 15/43 (48.4%) patients had a CD4 count < 200, and 35 (77.8%) were on ART. 30 (66.7%) patients met SIRS criteria within 24 hours of admission, and 27 (60%) required some form of oxygen supplementation during hospitalization, including 4 (8.9%) who required intubation. The average length of stay was 10.4 days (SD 12.5). 9 (20%) patients required an ICU stay, and 3 (6.7%) died. BMI > 30, CD4 count < 200, and viral load > 1000 were not associated with worse outcomes. Both a Charlson Comorbidity Index > 3 and the absence of ART were associated with need for ICU-level care. Conclusion. Viral load, CD4 count, and BMI were not correlated with differences in mortality or oxygen use in our study. Patients with higher Charlson Comorbidity Indices and patients who were not on ART at presentation were significantly more likely to require the ICU. Further study is needed to definitively determine factors affecting the outcomes of PLWH with SARS-CoV-2 infection.

4.
Nat Struct Mol Biol ; 29(3): 250-260, 2022 03.
Article in English | MEDLINE | ID: covidwho-1735263

ABSTRACT

The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA-dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex or RTC) associated with two copies of nsp13 (nsp132-RTC). One copy of nsp13 interacts with the template-RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backward on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here we use cryogenic-electron microscopy and molecular dynamics simulations to analyze the nsp132-RTC, revealing four distinct conformational states of the helicases. The results indicate a mechanism for the nsp132-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site.


Subject(s)
COVID-19 , SARS-CoV-2 , Cryoelectron Microscopy , Humans , RNA Helicases/chemistry , Viral Nonstructural Proteins/chemistry , Virus Replication
5.
Alzheimers Dement ; 17 Suppl 7: e056392, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1664383

ABSTRACT

BACKGROUND: Evidence suggests that brain-healthy behaviors, such as exercise, a Mediterranean diet, and cognitive/social stimulation, help protect against the risk of cognitive decline and dementia. We have been studying two interventions (health coach vs. physician education) that promote brain-healthy behaviors in patients with mild dementia (MD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and those at-risk. When COVID-19 occurred, we became interested in determining the extent to which the pandemic may have interfered with brain-healthy behaviors that participants had adopted. We designed a sub-study to investigate the pandemic's effects on adherence to brain-healthy behaviors in participants who completed either intervention in one of our two Brain Health Champion studies (BHC-1, BHC-2). METHOD: Participants from BHC-1 and BHC-2 were emailed questionnaires in September 2020. Of the 25 respondents, 15 (SCD:2, MCI:8, MD:5) were from BHC-1 and 10 (At-risk:5, MCI:5) were from BHC-2. Questionnaires measured changes from the start of the pandemic (March 2020) in self-reported physical activity, diet, and social/cognitive activities, as well as current sleep quality and feelings of anxiety and depression. RESULT: Results demonstrated that the pandemic had negatively impacted physical activity (p=.009) and social interactions (p<.001), with no significant changes in diet or cognitive activities. Additional data trends show that at-risk/SCD participants endorsed more feelings of anxiety and depression than MCI participants. At-risk/SCD participants also reported worse sleep quality than MCI participants (p=.036) across both studies and intervention arms. CONCLUSION: Our findings suggest that the pandemic significantly impacted activities typically done outside the home (social and physical activity), while activities that are typically done at home were less affected (Mediterranean diet adherence and cognitive activity). The pandemic seemed to diminish brain-healthy behaviors that participants likely gained from the interventions, demonstrating that clinical/research programs aimed at promoting brain health are strongly influenced by changes in the environment. Trends also show that there may be a direct relationship between anxiety/depression symptoms and sleep disruption in at-risk/SCD and MCI participants. More research is necessary to determine if these disruptions of behavior and sleep are temporary and will be well-compensated when COVID-19 restrictions are lifted.

6.
International Journal of Pharmaceutical Sciences Review and Research ; 71(1):45-51, 2021.
Article in English | EMBASE | ID: covidwho-1597927

ABSTRACT

Vaccine among people globally preparations must be made within countries for covid-19 vaccine safety surveillance on an urgent basis. Safety surveillance must be capable of investigating adverse event of special interest (AESI) and adverse event following immunization to determine a change in the benefit-risk profile of the vaccine. COVID-19 vaccine is the most important tool to stem the pandemic. WHO emergency use listing, while using regulatory pathway through national regulatory authorities. Vaccine safety communication plan should be developed. Expending the global vaccine safety system to meet the needs of covid-19 and other emergency and routine use vaccine is a priority currently. The protective efficacy and the short term and long-term side effect of the vaccine are of major concern. Various strategies have been designed the covid-19 pandemic. The highly infectious corona virus disease 2019 associate with me pathogenic severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has spread to become a global pandemic. The development of covid-19 vaccine is crucial for the world to return to pre-pandemic normalcy and the collective global effort has been invested into protective against SARS-CoV2.

7.
Nature ; 602(7897): 481-486, 2022 02.
Article in English | MEDLINE | ID: covidwho-1585829

ABSTRACT

Humans have infected a wide range of animals with SARS-CoV-21-5, but the establishment of a new natural animal reservoir has not been observed. Here we document that free-ranging white-tailed deer (Odocoileus virginianus) are highly susceptible to infection with SARS-CoV-2, are exposed to multiple SARS-CoV-2 variants from humans and are capable of sustaining transmission in nature. Using real-time PCR with reverse transcription, we detected SARS-CoV-2 in more than one-third (129 out of 360, 35.8%) of nasal swabs obtained from O. virginianus in northeast Ohio in the USA during January to March 2021. Deer in six locations were infected with three SARS-CoV-2 lineages (B.1.2, B.1.582 and B.1.596). The B.1.2 viruses, dominant in humans in Ohio at the time, infected deer in four locations. We detected probable deer-to-deer transmission of B.1.2, B.1.582 and B.1.596 viruses, enabling the virus to acquire amino acid substitutions in the spike protein (including the receptor-binding domain) and ORF1 that are observed infrequently in humans. No spillback to humans was observed, but these findings demonstrate that SARS-CoV-2 viruses have been transmitted in wildlife in the USA, potentially opening new pathways for evolution. There is an urgent need to establish comprehensive 'One Health' programmes to monitor the environment, deer and other wildlife hosts globally.


Subject(s)
Animals, Wild/virology , COVID-19/veterinary , Deer/virology , Phylogeny , SARS-CoV-2/isolation & purification , Viral Zoonoses/transmission , Viral Zoonoses/virology , Amino Acid Sequence , Amino Acid Substitution , Animals , COVID-19/epidemiology , COVID-19/transmission , Evolution, Molecular , Humans , Male , Ohio/epidemiology , One Health/trends , SARS-CoV-2/chemistry , SARS-CoV-2/classification , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Viral Zoonoses/epidemiology
8.
mSphere ; 6(6): e0071121, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1546463

ABSTRACT

The COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities, their antiviral properties remain poorly explored. Using a cell-based SARS-CoV-2 infection assay, we screened culture broth extracts from a collection of phylogenetically diverse human-associated bacteria for the production of small molecules with antiviral activity. Bioassay-guided fractionation uncovered three bacterial metabolites capable of inhibiting SARS-CoV-2 infection. This included the nucleoside analogue N6-(Δ2-isopentenyl)adenosine, the 5-hydroxytryptamine receptor agonist tryptamine, and the pyrazine 2,5-bis(3-indolylmethyl)pyrazine. The most potent of these, N6-(Δ2-isopentenyl)adenosine, had a 50% inhibitory concentration (IC50) of 2 µM. These natural antiviral compounds exhibit structural and functional similarities to synthetic drugs that have been clinically examined for use against COVID-19. Our discovery of structurally diverse metabolites with anti-SARS-CoV-2 activity from screening a small fraction of the bacteria reported to be associated with the human microbiome suggests that continued exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections. IMPORTANCE The continued prevalence of COVID-19 and the emergence of new variants has once again put the spotlight on the need for the identification of SARS-CoV-2 antivirals. The human microbiome produces an array of small molecules with bioactivities (e.g., host receptor ligands), but its ability to produce antiviral small molecules is relatively underexplored. Here, using a cell-based screening platform, we describe the isolation of three microbiome-derived metabolites that are able to prevent SARS-CoV-2 infection in vitro. These molecules display structural similarities to synthetic drugs that have been explored for the treatment of COVID-19, and these results suggest that the microbiome may be a fruitful source of the discovery of small molecules with antiviral activities.


Subject(s)
Antiviral Agents/pharmacology , Bacteria/metabolism , Culture Media/chemistry , Metabolic Networks and Pathways , Microbiota/physiology , SARS-CoV-2/drug effects , Symbiosis/physiology , Bacteria/chemistry , Bacteria/classification , Bacteria/growth & development , Biological Assay , Cell Line, Tumor , Culture Media/pharmacology , Humans , Molecular Docking Simulation , Protease Inhibitors/pharmacology , Protein Binding
9.
Non-conventional in English | [Unspecified Source], Grey literature | ID: grc-750506

ABSTRACT

SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated-transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The Nidovirus-order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12-thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.

10.
Preprint in English | bioRxiv | ID: ppbiorxiv-468168

ABSTRACT

The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex, or RTC) associated with two copies of nsp13 (nsp132-RTC). One copy of nsp13 interacts with the template RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backwards on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here, we use cryo-electron microscopy and molecular dynamics simulations to analyze the nsp132-RTC, revealing four distinct conformational states of the helicases. The results suggest a mechanism for the nsp132-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site.

11.
Preprint in English | bioRxiv | ID: ppbiorxiv-467308

ABSTRACT

Human-to-animal spillover of SARS-CoV-2 virus has occurred in a wide range of animals, but thus far, the establishment of a new natural animal reservoir has not been detected. Here, we detected SARS-CoV-2 virus using rRT-PCR in 129 out of 360 (35.8%) free-ranging white-tailed deer (Odocoileus virginianus) from northeast Ohio (USA) sampled between January-March 2021. Deer in 6 locations were infected with at least 3 lineages of SARS-CoV-2 (B.1.2, B.1.596, B.1.582). The B.1.2 viruses, dominant in Ohio at the time, spilled over multiple times into deer populations in different locations. Deer-to-deer transmission may have occurred in three locations. The establishment of a natural reservoir of SARS-CoV-2 in white-tailed deer could facilitate divergent evolutionary trajectories and future spillback to humans, further complicating long-term COVID-19 control strategies. One-Sentence SummaryA significant proportion of SARS-CoV-2 infection in free-ranging US white-tailed deer reveals a potential new reservoir.

12.
Emerg Infect Dis ; 27(10): 2720-2723, 2021.
Article in English | MEDLINE | ID: covidwho-1486743

ABSTRACT

We report persistent severe acute respiratory syndrome coronavirus 2 infection in a patient with HIV/AIDS; the virus developed spike N terminal domain and receptor binding domain neutralization resistance mutations. Our findings suggest that immunocompromised patients can harbor emerging variants of severe acute respiratory syndrome coronavirus 2.


Subject(s)
Acquired Immunodeficiency Syndrome , COVID-19 , Humans , Mutation , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
14.
mBio ; 12(5): e0252721, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1476394

ABSTRACT

Respiratory viruses such as SARS-CoV-2 are transmitted in respiratory droplets and aerosol particles, which are released during talking, breathing, coughing, and sneezing. Noncontact transmission of SARS-CoV-2 has been demonstrated, suggesting transmission via virus carried through the air. Here, we demonstrate that golden Syrian hamsters produce infectious SARS-CoV-2 in aerosol particles prior to and concurrent with the onset of mild clinical signs of disease. The average emission rate in this study was 25 infectious virions/hour on days 1 and 2 postinoculation, with average viral RNA levels 200-fold higher than infectious virus in aerosol particles. The majority of virus was contained within particles <5 µm in size. Thus, we provide direct evidence that, in hamsters, SARS-CoV-2 is an airborne virus. IMPORTANCE SARS-CoV-2 is a respiratory virus and has been isolated from the air near COVID-19 patients. Here, using a hamster model of infection, we demonstrate that SARS-CoV-2 is emitted in aerosol particles prior to and concurrent with the onset of mild disease. Virus is contained primarily within aerosol particles <5 µm in size, which can remain airborne and be inhaled. These findings indicate that SARS-CoV-2 is an airborne virus and support the use of ventilation to reduce SARS-CoV-2 transmission.


Subject(s)
Aerosols , COVID-19/transmission , SARS-CoV-2/pathogenicity , Animals , COVID-19/metabolism , Chlorocebus aethiops , Cricetinae , Mesocricetus , Real-Time Polymerase Chain Reaction , Vero Cells
15.
Healthc (Amst) ; 9(4): 100589, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1458725

ABSTRACT

Food insecurity is defined by limited access to adequate food. As a result, it is associated with chronic disease for millions of Americans. Healthcare systems take responsibility for improving patient health and thus are well positioned to create food security interventions that improve health. Given that dietary recommendations now emphasize plant-based foods (such as vegetables, fruits, legumes, and whole grains), interventions could prioritize distributing plant-based foods that promote health and reduce food insecurity. We developed a plant-based food pantry at the Massachusetts General Hospital Revere Healthcare Center, an academic medical center-affiliated community clinic that serves many patients with food insecurity. We partnered with a local food bank and used a color-coded nutrition ranking system to prioritize healthy foods. What began as a pilot program for patients with food insecurity and chronic disease expanded to serve the entire clinic population in response to rising community level food insecurity resulting from the COVID-19 pandemic. We developed and modified a workflow that provided an average of 384 recipients (i.e., patients and their household members) with food monthly during the 10-month study period. A total of 117,742 pounds of food was distributed. Next steps for the food pantry will include investigating health outcomes, assessing patient satisfaction with plant-based foods, and securing sustainable funding. Our experience can be used to guide other health organizations interested in the intersection of food security and chronic disease management.


Subject(s)
COVID-19 , Food Assistance , Academic Medical Centers , Food Supply , Health Promotion , Hospitals, General , Humans , Hunger , Pandemics , SARS-CoV-2 , United States
16.
Infect Prev Pract ; 3(4): 100170, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1446728

ABSTRACT

BACKGROUND: As researchers race to understand the nature of COVID-19 transmission, healthcare institutions must treat COVID-19 patients while also safeguarding the health of staff and other patients. One aspect of this process involves mitigating aerosol transmission of the SARS-CoV2 virus. The U.S. Centers for Disease Control and Prevention (CDC) provides general guidance on airborne contaminant removal, but directly measuring aerosol clearance in clinical rooms provides empirical evidence to guide clinical procedure. AIM: We present a risk-assessment approach to empirically measuring and certifying the aerosol clearance time (ACT) in operating and procedure rooms to improve hospital efficiency while also mitigating the risk of nosocomial infection. METHODS: Rooms were clustered based on physical and procedural parameters. Sample rooms from each cluster were randomly selected and tested by challenging the room with aerosol and monitoring aerosolized particle concentration until 99.9% clearance was achieved. Data quality was analysed and aerosol clearance times for each cluster were determined. FINDINGS: Of the 521 operating and procedure rooms considered, 449 (86%) were issued a decrease in clearance time relative to CDC guidance, 32 (6%) had their clearance times increased, and 40 (8%) remained at guidance. The average clearance time change of all rooms assessed was a net reduction of 27.8%. CONCLUSION: The process described here balances the need for high-quality, repeatable data with the burden of testing in a functioning clinical setting. Implementation of this approach resulted in a reduction in clearance times for most clinical rooms, thereby improving hospital efficiency while also safeguarding patients and staff.

17.
PLoS One ; 16(9): e0257622, 2021.
Article in English | MEDLINE | ID: covidwho-1438350

ABSTRACT

OBJECTIVES: Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates. METHODS: Using data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata. RESULTS: Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts. CONCLUSIONS: Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.


Subject(s)
COVID-19 , Health Status Disparities , Hospitalization , Minority Groups , SARS-CoV-2 , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/therapy , Female , Humans , Male , Middle Aged , United States/epidemiology
18.
Enzymes ; 49: 1-37, 2021.
Article in English | MEDLINE | ID: covidwho-1370416

ABSTRACT

The ongoing Covid-19 pandemic has spurred research in the biology of the nidovirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Much focus has been on the viral RNA synthesis machinery due to its fundamental role in viral propagation. The central and essential enzyme of the RNA synthesis process, the RNA-dependent RNA polymerase (RdRp), functions in conjunction with a coterie of viral-encoded enzymes that mediate crucial nucleic acid transactions. Some of these enzymes share common features with other RNA viruses, while others play roles unique to nidoviruses or CoVs. The RdRps are proven targets for viral pathogens, and many of the other nucleic acid processing enzymes are promising targets. The purpose of this review is to summarize recent advances in our understanding of the mechanisms of RNA synthesis in CoVs. By reflecting on these studies, we hope to emphasize the remaining gaps in our knowledge. The recent onslaught of structural information related to SARS-CoV-2 RNA synthesis, in combination with previous structural, genetic and biochemical studies, have vastly improved our understanding of how CoVs replicate and process their genomic RNA. Structural biology not only provides a blueprint for understanding the function of the enzymes and cofactors in molecular detail, but also provides a basis for drug design and optimization. The concerted efforts of researchers around the world, in combination with the renewed urgency toward understanding this deadly family of viruses, may eventually yield new and improved antivirals that provide relief to the current global devastation.


Subject(s)
RNA, Viral , SARS-CoV-2/genetics , RNA, Viral/biosynthesis , RNA, Viral/genetics , RNA-Dependent RNA Polymerase/genetics
19.
Preprint in English | bioRxiv | ID: ppbiorxiv-455702

ABSTRACT

Respiratory viruses such as SARS-CoV-2 are transmitted in respiratory droplets and aerosols, which are released during talking, breathing, coughing, and sneezing. Non-contact transmission of SARS-CoV-2 has been demonstrated, suggesting transmission in aerosols. Here we demonstrate that golden Syrian hamsters emit infectious SARS-CoV-2 in aerosols, prior to and concurrent with the onset of mild clinical signs of disease. The average emission rate is 25 infectious virions/hour on days 1 and 2 post-inoculation, with average viral RNA levels 200-fold higher than infectious virus in aerosols. Female hamsters have delayed kinetics of viral shedding in aerosols compared to male hamsters, with peak viral emission for females on dpi 2 and for males on dpi 1. The majority of virus is contained within aerosols <8 {micro}m in size. Thus, we provide direct evidence that, in hamsters, SARS-CoV-2 is an airborne virus.

20.
Biointerface Research in Applied Chemistry ; 12(2):1385-1396, 2022.
Article in English | Scopus | ID: covidwho-1328442

ABSTRACT

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro;PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp;PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro . Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19. © 2021 by the authors.

SELECTION OF CITATIONS
SEARCH DETAIL