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1.
Southeast Asian Journal of Tropical Medicine and Public Health ; 53(5):513-529, 2022.
Article in English | Web of Science | ID: covidwho-2109607

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19. Identification of virus lineages is key to tracking the chains of transmission and for monitoring variants of interest as well as variants of concern. This study aimed to develop and validate a cost-effective method to determine SARS-CoV-2 lineages of virus samples from the first wave of the pandemic in Thailand (January -May 2020). A lineage-specific single nucleotide polymorphism (SNP) genotyping panel of SARS-CoV-2 was designed based on genomic surveillance data generated in the first wave. Viral RNA specimens obtained from the Department of Pathology, Faculty of Medicine Ramathibodi Hospital were analyzed by a MassARRAY (R) platform in comparison to a next generation sequencing of the virus genome. The MassARRAY (R) system was able to identify the SARS-CoV-2 lineages with high accuracy supporting its application as a rapid and cost-effective method for identification of circulating COVID-1 9 variants in the country, and has the ability to accommodate new SARS-CoV-2 variants by simple modifications of the assay protocol.

2.
Vojnosanitetski Pregled ; 79(9):849-856, 2022.
Article in English | Web of Science | ID: covidwho-2109592

ABSTRACT

Background/Aim. Coronavirus disease 2019 (COVID-19) is a predominantly respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to determine whether there were parameters that could predict the development of a severe clinical picture and fatal outcomes in COVID-19 patients. Methods. The study involved 632 patients treated at the Clinic for Infectious Diseases, University Clinical Center Kragujevac, from June 2020 to February 2021. All patients were divided into two groups according to the need for ox-ygen therapy (Sat 02 < 94 %). Results. Our results showed that high body mass index (BMI) was singled out as a risk factor for the development of a severe clinical picture (BMI, ORadjusted = 1.263;95% CI = 1.117 - 1.427;p < 0.001). Pro -thrombin time (ORadjusted = 1.170;95% CI = 1.004 -1.364;p = 0.045), as well as low albumin values (ORadjusted = 0.878;95% CI = 0.804 -0.958;p = 0.003), had a predictive signifi-cance for the development of a severe clinical picture. Factors that were of predictive importance in patients with fatal outcomes were C-reactive protein (CRP) (ORadjusted = 1.010;95% CI = 1.001 - 1.019;p = 0.031), lactate dehydrogenase (LDH) (ORadjusted = 1.004;95% CI = 1.001 - 1.006;p = 0.002), and X-ray of the lungs (ORadjusted = 1.394;95% CI = 1.170 - 1.661;p < 0.001). Conclusion. The study showed that routine, clinical laboratory parameters can be important in the early detection of patients with a potentially severe clinical picture and fatal outcomes. In patients with a mild clinical picture, CRP, LDH, ferritin, and serum albumin lev-els may timely indicate disease progression. Monitoring these parameters is of essential importance for the timely clinical assessment of patients with COVID-19 and, thus, the prompt application of adequate therapeutic protocols in the treatment of these patients.

3.
Int J Environ Res Public Health ; 19(22)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2110072

ABSTRACT

BACKGROUND: Several reports from around the world have reported that some patients who have recovered from COVID-19 have experienced a range of persistent or new clinical symptoms after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. METHODS: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (<2500 m) and high altitude (>2500 m). RESULTS: Overall, 1100 (52.3%) responders claimed to have Long-COVID symptoms after SARS-CoV-2 infection. Most of these were reported by women (64.0%); the most affected group was young adults between 21 to 40 years (68.5%), and most long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of symptoms was observed in the group that received less than 2 doses. CONCLUSIONS: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 21-40, are more likely to describe Long-COVID. We also found that living at a high altitude was associated with higher reports of mood changes, tachycardia, decreased libido, insomnia, and palpitations compared to lowlanders. Finally, we found a greater risk to report Long-COVID symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.


Subject(s)
Altitude , COVID-19 , Young Adult , Humans , Female , COVID-19/epidemiology , Cross-Sectional Studies , SARS-CoV-2
4.
Diseases ; 10(4)2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2109981

ABSTRACT

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into a pandemic affecting virtually every country in the world. We evaluated the demographic, clinical, laboratory, and all-cause mortality of moderate and severe COVID-19 patients admitted to a tertiary care hospital in Oman during the different COVID-19 waves and variant types. (2) Methods: A case-series retrospective study was carried out between 12 March 2020 and 30 June 2022. All adults over the age of 18 with laboratory-confirmed COVID-19 were enrolled. Analyses were performed using univariate and multivariate statistics. (3) Results: A total of 1462 confirmed cases enrolled with the mean age of the cohort was 55 ± 17 years with significant differences among the groups (p = 0.006). A total of 63% and 80% of the patients were males and citizens of Oman, respectively. Patients infected with the Alpha COVID-19 variant type were more likely to have acute respiratory distress syndrome (ARDS) (p < 0.001), stay longer in the hospital (p < 0.001), and get admitted to the intensive care unit (ICU) (p < 0.001). At the same time, those who had the Omicron COVID-19 type were more likely to have renal impairment (p < 0.001) and less likely to be associated with non-invasive ventilation (NIV) (p = 0.001) compared with other COVID-19 variant types. The Delta (adjusted odds ratio (aOR), 1.8; 95% confidence interval (CI): 1.22-2.66; p = 0.003) and Omicron (aOR, 1.88; 95% CI: 1.09-3.22; p = 0.022) COVID-19 variant types were associated with higher all-cause mortality when compared to the initial COVID-19 variant. Old age (aOR, 1.05; 95% CI: 1.04-1.06; p < 0.001), the presence of respiratory disease (aOR, 1.58; 95% CI: 1.02-2.44; p = 0.04), ICU admission (aOR, 3.41; 95% CI: 2.16-5.39; p < 0.001), lower eGFR (aOR, 1.61; 95% CI: 1.17-2.23; p = 0.004), and ARDS (aOR, 5.75; 95% CI: 3.69-8.98; p < 0.001) were also associated with higher mortality while NIV requirements were associated with lower odds of dying (aOR, 0.65; 95% CI: 0.46-0.91; p = 0.012). (4) Conclusions: Alpha and Delta variants were associated with a longer hospital stay, need for intensive care, mechanical ventilation, and increased mortality. Old age, cardiac renal dysfunction were commonly associated with Omicron variants. Large-scale national studies to further assess the risk factors for mortality related to COVID-19 waves are warranted.

5.
Children (Basel) ; 9(11)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2109958

ABSTRACT

BACKGROUND: This study aims to describe the observable symptoms of children with COVID-19 infection and analyze access to real-time polymerase chain reaction (RT-PCR) testing among children seeking care in Yemen. METHOD: In the period of March 2020-February 2022, data were obtained from 495 children suspected to have been infected with COVID-19 (from a larger register of 5634 patients) from the Diseases Surveillance and Infection Control Department at the Ministry of Public Health and Population in Aden, Yemen. RESULTS: Overall, 21.4% of the children with confirmed COVID-19 infection were asymptomatic. Fever (71.4%) and cough (67.1%) were the most frequently reported symptoms among children, and children were less likely to have fever (p < 0.001), sore throat (p < 0.001) and cough (p < 0.001) compared to adults. A lower frequency of COVID-19-associated symptoms was reported among children with positive RT-PCR tests compared to children with negative tests. A lower rate of testing was conducted among children (25%) compared to adults (61%). Fewer tests were carried out among children years (11%) compared to other age groups (p < 0.001), for children from other nationalities (4%) compared to Yemeni children (p < 0.001) and for girls (21%) compared to boys (30%) (p 0.031). CONCLUSION: Understanding and addressing the cause of these disparities and improving guidelines for COVID-19 screening among children will improve access to care and control of the COVID-19 pandemic.

6.
Cells ; 11(19)2022 Sep 22.
Article in English | MEDLINE | ID: covidwho-2109954

ABSTRACT

Although dementia is a heterogenous group of diseases, inflammation has been shown to play a central role in all of them and provides a common link in their pathology. This review aims to highlight the importance of immune response in the most common types of dementia. We describe molecular aspects of pro-inflammatory signaling and sources of inflammatory activation in the human organism, including a novel infectious agent, SARS-CoV-2. The role of glial cells in neuroinflammation, as well as potential therapeutic approaches, are then discussed. Peripheral immune response and increased cytokine production, including an early surge in TNF and IL-1ß concentrations activate glia, leading to aggravation of neuroinflammation and dysfunction of neurons during COVID-19. Lifestyle factors, such as diet, have a large impact on future cognitive outcomes and should be included as a crucial intervention in dementia prevention. While the use of NSAIDs is not recommended due to inconclusive results on their efficacy and risk of side effects, the studies focused on the use of TNF antagonists as the more specific target in neuroinflammation are still very limited. It is still unknown, to what degree neuroinflammation resulting from COVID-19 may affect neurodegenerative process and cognitive functioning in the long term with ongoing reports of chronic post-COVID complications.


Subject(s)
COVID-19 , Dementia , Anti-Inflammatory Agents, Non-Steroidal , Cytokines , Humans , Neuroinflammatory Diseases , Pandemics , SARS-CoV-2 , Tumor Necrosis Factor Inhibitors
7.
Cancers (Basel) ; 14(22)2022 Nov 09.
Article in English | MEDLINE | ID: covidwho-2109948

ABSTRACT

BACKGROUND: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. METHODS: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. RESULTS: A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum-antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. CONCLUSIONS: Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed.

8.
Brain Sci ; 12(11)2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2109938

ABSTRACT

The COVID-19 virus frequently causes neurological complications. These have been described in various forms in adults and children. Headache, seizures, coma, and encephalitis are some of the manifestations of SARS-CoV-2-induced neurological impairment. Recent publications have revealed important aspects of viral pathophysiology and its involvement in nervous-system impairment in humans. We evaluated the latest literature describing the relationship between COVID-19 infection and the central nervous system. We searched three databases for observational and interventional studies in adults published between December 2019 and September 2022. We discussed in narrative form the neurological impairment associated with COVID-19, including clinical signs and symptoms, imaging abnormalities, and the pathophysiology of SARS-CoV2-induced neurological damage.

9.
Biosensors (Basel) ; 12(11)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2109936

ABSTRACT

Quick label-free virus screening and highly sensitive analytical tools/techniques are becoming extremely important in a pandemic. In this study, we developed a biosensing device based on the silicon nanoribbon multichannel and dielectrophoretic controlled sensors functionalized with SARS-CoV-2 spike antibodies for the use as a platform for the detection and studding of properties of viruses and their protein components. Replicatively defective viral particles based on vesicular stomatitis viruses and HIV-1 were used as carrier molecules to deliver the target SARS-CoV-2 spike S-proteins to sensory elements. It was shown that fully CMOS-compatible nanoribbon sensors have the subattomolar sensitivity and dynamic range of 4 orders. Specific interaction between S-proteins and antibodies leads to the accumulation of the negative charge on the sensor surface. Nonspecific interactions of the viral particles lead to the positive charge accumulation. It was shown that dielectrophoretic controlled sensors allow to estimate the effective charge of the single virus at the sensor surface and separate it from the charge associated with the binding of target proteins with the sensor surface.


Subject(s)
Biosensing Techniques , COVID-19 , Nanotubes, Carbon , Humans , SARS-CoV-2 , Biosensing Techniques/methods , Pandemics , Antibodies, Viral
10.
Biosensors (Basel) ; 12(11)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2109935

ABSTRACT

Worldwide infection due to SARS-CoV-2 revealed that short-time and extremely high-sensitivity detection of nucleic acids is a crucial technique for human beings. Polymerase chain reactions have been mainly used for the SARS-CoV-2 detection over the years. However, an advancement in quantification of the detection and shortening runtime is important for present and future use. Here, we report a rapid detection scheme that is a combination of nucleic acid amplification and a highly efficient fluorescence biosensor, that is, a metasurface biosensor composed of a pair of an all-dielectric metasurface and a microfluidic transparent chip. In the present scheme, we show a series of proof-of-concept experimental results that the metasurface biosensors detected amplicons originating from attomolar SARS-CoV-2 nucleic acids and that the amplification was implemented within 1 h. Furthermore, this detection capability substantially satisfies an official requirement of 100 RNA copies/140 µL, which is a criterion for the reliable infection tests.


Subject(s)
Biosensing Techniques , COVID-19 , Nucleic Acids , Humans , SARS-CoV-2 , COVID-19/diagnosis , Sensitivity and Specificity , Nucleic Acid Amplification Techniques/methods , Molecular Diagnostic Techniques/methods
11.
Biosensors (Basel) ; 12(11)2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2109934

ABSTRACT

Rapid and cost-effective diagnostic tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a critical and valuable weapon for the coronavirus disease 2019 (COVID-19) pandemic response. SARS-CoV-2 invasion is primarily mediated by human angiotensin-converting enzyme 2 (hACE2). Recent developments in ACE2-based SARS-CoV-2 detection modalities accentuate the potential of this natural host-virus interaction for developing point-of-care (POC) COVID-19 diagnostic systems. Although research on harnessing ACE2 for SARS-CoV-2 detection is in its infancy, some interesting biosensing devices have been developed, showing the commercial viability of this intriguing new approach. The exquisite performance of the reported ACE2-based COVID-19 biosensors provides opportunities for researchers to develop rapid detection tools suitable for virus detection at points of entry, workplaces, or congregate scenarios in order to effectively implement pandemic control and management plans. However, to be considered as an emerging approach, the rationale for ACE2-based biosensing needs to be critically and comprehensively surveyed and discussed. Herein, we review the recent status of ACE2-based detection methods, the signal transduction principles in ACE2 biosensors and the development trend in the future. We discuss the challenges to development of ACE2-biosensors and delineate prospects for their use, along with recommended solutions and suggestions.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , COVID-19/diagnosis , SARS-CoV-2 , Peptidyl-Dipeptidase A/physiology , Pandemics
12.
Biomedicines ; 10(11)2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2109932

ABSTRACT

Throughout the pandemic, serological assays have been revealed as crucial for detecting previous exposures to the virus and determining the timing of antibody maintenance after vaccination or natural infection. This study aimed to develop an optimized enzyme-linked immunosorbent assay (ELISA)-based serology, which could be used in case of reagent shortages, such as that occurred in the beginning of this health emergency. As a result, we present a high-sensitive immunoassay for the determination of IgG levels in venous serum samples, using 2 µg/mL antigen (receptor-binding domain of the spike protein S1) for coating the plate and utilizing human samples at a dilution 1:1000. This method showed non-inferiority features versus a commercial kit, is less expensive, and has a higher spectrophotometric range that allows for a better quantification of the antibody titers. The optical density values before and after heating venous serum samples at 56 °C during 30 min was quite similar, showing that heat inactivation can be used to reduce the biohazardous risks while handling samples. Furthermore, we show that finger-stick capillary blood samples can also serve as a suitable source for IgG detection, bypassing the need for serum isolation and being suitable for point-of-care application (Pearson's coefficient correlation with capillary serum was 0.95, being statistically significant).

13.
Biomedicines ; 10(11)2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2109931

ABSTRACT

Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin's lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.

14.
Biomolecules ; 12(11)2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2109925

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently widespread throughout the world, accompanied by a rising number of people infected and breakthrough infection of variants, which make the virus highly transmissible and replicable. A comprehensive understanding of the molecular virological events and induced immunological features during SARS-CoV-2 replication can provide reliable targets for vaccine and drug development. Among the potential targets, subgenomic RNAs and their encoded proteins involved in the life cycle of SARS-CoV-2 are extremely important in viral duplication and pathogenesis. Subgenomic RNAs employ a range of coping strategies to evade immune surveillance from replication to translation, which allows RNAs to synthesize quickly, encode structural proteins efficiently and complete the entire process of virus replication and assembly successfully. This review focuses on the characteristics and functions of SARS-CoV-2 subgenomic RNAs and their encoded proteins and explores in depth the role of subgenomic RNAs in the replication and infection of host cells to provide important clues to the mechanism of COVID-19 pathogenesis.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , RNA , Virus Replication/genetics , Viral Proteins/metabolism
15.
Biomolecules ; 12(11)2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2109924

ABSTRACT

Gold compounds have a long tradition in medicine and offer many opportunities for new therapeutic applications. Herein, we evaluated the lead compound Auranofin and five related gold(I) complexes as possible inhibitors of SARS-CoV-2 Main Protease (SARS-CoV-2 Mpro), a validated drug target for the COVID-19 disease. The investigational panel of gold compounds included Auranofin; three halido analogues, i.e., Au(PEt3)Cl, Au(PEt3)Br, and Au(PEt3)I; and two gold carbene complexes, i.e., Au(NHC)Cl and [Au(NHC)2]PF6. Notably, all these gold compounds, with the only exception of [Au(NHC)2]PF6, turned out to be potent inhibitors of the catalytic activity of SARS-CoV-2 Mpro: the measured Ki values were in the range 2.1-0.4 µM. The reactions of the various gold compounds with SARS-CoV-2 Mpro were subsequently investigated through electrospray ionization (ESI) mass spectrometry (MS) upon a careful optimization of the experimental conditions; the ESI MS spectra provided clear evidence for the formation of tight metallodrug-protein adducts and for the coordination of well defined gold-containing fragments to the SARS-CoV-2 Mpro, again with the only exception of [Au(NHC)2]PF6, The metal-protein stoichiometry was unambiguously determined for the resulting species. The crystal structures of the metallodrug- Mpro adducts were solved in the case of Au(PEt3)Br and Au(NHC)Cl. These crystal structures show that gold coordination occurs at the level of catalytic Cys 145 in the case of Au(NHC)Cl and at the level of both Cys 145 and Cys 156 for Au(PEt3)Br. Tight coordination of gold atoms to functionally relevant cysteine residues is believed to represent the true molecular basis of strong enzyme inhibition.


Subject(s)
Auranofin , COVID-19 , Humans , Auranofin/pharmacology , Viral Proteins/chemistry , SARS-CoV-2 , COVID-19/drug therapy , Gold Compounds/pharmacology , Cysteine , Gold/pharmacology
16.
Biomolecules ; 12(11)2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2109923

ABSTRACT

BACKGROUND: SARS-CoV-2 has undergone mutations, yielding clinically relevant variants. HYPOTHESIS: We hypothesized that in SARS-CoV-2, two highly conserved Orf3a and E channels directly related to the virus replication were a target for the detection and inhibition of the viral replication, independent of the variant, using FDA-approved ion channel modulators. METHODS: A combination of a fluorescence potassium ion assay with channel modulators was developed to detect SARS-CoV-2 Orf3a/E channel activity. Two FDA-approved drugs, amantadine (an antiviral) and amitriptyline (an antidepressant), which are ion channel blockers, were tested as to whether they inhibited Orf3a/E channel activity in isolated virus variants and in nasal swab samples from COVID-19 patients. The variants were confirmed by PCR sequencing. RESULTS: In isolated SARS-CoV-2 Alpha, Beta, and Delta variants, the channel activity of Orf3a/E was detected and inhibited by emodin and gliclazide (IC50 = 0.42 mM). In the Delta swab samples, amitriptyline and amantadine inhibited the channel activity of viral proteins, with IC50 values of 0.73 mM and 1.11 mM, respectively. In the Omicron swab samples, amitriptyline inhibited the channel activity, with an IC50 of 0.76 mM. CONCLUSIONS: We developed an efficient method to screen FDA-approved ion channel modulators that could be repurposed to detect and inhibit SARS-CoV-2 viral replication, independent of variants.


Subject(s)
COVID-19 , Ion Channels , SARS-CoV-2 , Humans , Amantadine/pharmacology , Amitriptyline/pharmacology , COVID-19/drug therapy , Ion Channels/antagonists & inhibitors , SARS-CoV-2/drug effects , Drug Evaluation, Preclinical , Drug Repositioning
17.
Biomolecules ; 12(11)2022 Nov 10.
Article in English | MEDLINE | ID: covidwho-2109922

ABSTRACT

With its fast-paced mutagenesis, the SARS-CoV-2 Omicron variant has threatened many societies worldwide. Strategies for predicting mutagenesis such as the computational prediction of SARS-CoV-2 structural diversity and its interaction with the human receptor will greatly benefit our understanding of the virus and help develop therapeutics against it. We aim to use protein structure prediction algorithms along with molecular docking to study the effects of various mutations in the Receptor Binding Domain (RBD) of the SARS-CoV-2 and its key interactions with the angiotensin-converting enzyme 2 (ACE-2) receptor. The RBD structures of the naturally occurring variants of SARS-CoV-2 were generated from the WUHAN-Hu-1 using the trRosetta algorithm. Docking (HADDOCK) and binding analysis (PRODIGY) between the predicted RBD sequences and ACE-2 highlighted key interactions at the Receptor-Binding Motif (RBM). Further mutagenesis at conserved residues in the Original, Delta, and Omicron variants (P499S and T500R) demonstrated stronger binding and interactions with the ACE-2 receptor. The predicted T500R mutation underwent some preliminary tests in vitro for its binding and transmissibility in cells; the results correlate with the in-silico analysis. In summary, we suggest conserved residues P499 and T500 as potential mutation sites that could increase the binding affinity and yet do not exist in nature. This work demonstrates the use of the trRosetta algorithm to predict protein structure and future mutations at the RBM of SARS-CoV-2, followed by experimental testing for further efficacy verification. It is important to understand the protein structure and folding to help develop potential therapeutics.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/genetics , Spike Glycoprotein, Coronavirus/chemistry , Molecular Docking Simulation , Peptidyl-Dipeptidase A/chemistry , Receptors, Virus , Protein Binding , Mutation , Protein Folding
18.
Antioxidants (Basel) ; 11(11)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2109909

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus was first recognized in late 2019 and remains a significant threat. We therefore assessed the use of local methylene blue photodynamic viral inactivation (MB-PDI) in the oral and nasal cavities, in combination with the systemic anti-viral, anti-inflammatory and antioxidant actions of orally ingested methylene blue (MB) and photobiomodulation (PBM) for COVID-19 disease. The proposed protocol leverages the separate and combined effects of MB and 660nm red light emitted diode (LED) to comprehensively address the pathophysiological sequelae of COVID-19. A total of eight pilot subjects with COVID-19 disease were treated in the Bahamas over the period June 2021-August 2021, using a remote care program that was developed for this purpose. Although not a pre-requisite for inclusion, none of the subjects had received any COVID-19 vaccination prior to commencing the study. Clinical outcome assessment tools included serial cycle threshold measurements as a surrogate estimate of viral load; serial online questionnaires to document symptom response and adverse effects; and a one-year follow-up survey to assess long-term outcomes. All subjects received MB-PDI to target the main sites of viral entry in the nose and mouth. This was the central component of the treatment protocol with the addition of orally ingested MB and/or PBM based on clinical requirements. The mucosal surfaces were irradiated with 660 nm LED in a continuous emission mode at energy density of 49 J/cm2 for PDI and 4.9 J/cm2 for PBM. Although our pilot subjects had significant co-morbidities, extremely high viral loads and moderately severe symptoms during the Delta phase of the pandemic, the response to treatment was highly encouraging. Rapid reductions in viral loads were observed and negative PCR tests were documented within a median of 4 days. These laboratory findings occurred in parallel with significant clinical improvement, mostly within 12-24 h of commencing the treatment protocol. There were no significant adverse effects and none of the subjects who completed the protocol required in-patient hospitalization. The outcomes were similarly encouraging at one-year follow-up with virtual absence of "long COVID" symptoms or of COVID-19 re-infection. Our results indicate that the protocols may be a safe and promising approach to challenging COVID-19 disease. Moreover, due its broad spectrum of activity, this approach has the potential to address the prevailing and future COVID-19 variants and other infections transmitted via the upper respiratory tract. Extensive studies with a large cohort are warranted to validate our results.

19.
Antibiotics (Basel) ; 11(11)2022 Nov 13.
Article in English | MEDLINE | ID: covidwho-2109907

ABSTRACT

The first case of SARS-CoV-2 infection was reported in December 2019. Due to the rapid spread of the disease and the lack of adequate therapy, the use of plants that have a long history in the treatment of viral infections has often been considered. The aim of this paper is to provide a brief review of the literature on the use of phytochemicals during the new pandemic. An extensive search of published works was performed through platforms Google Scholar, PubMed, Science Direct, Web of Science and Clinicaltrials.gov. Numerous preclinical studies on the use of phytochemicals (quercetin, curcumin, baicalin, kaempferol, resveratrol, glycyrrhizin, lycorine, colchicine) against SARS-CoV-2 have shown that these components can be effective in the prevention and treatment of this infection. Clinical research has proven that the use of black cumin and green propolis as well as quercetin has positive effects. As for other phytochemicals, in addition to preclinical testing which has already been carried out, it would be necessary to conduct clinical tests in order to assert their effectiveness. For those phytochemicals whose clinical efficacy has been proven, it would be necessary to conduct research on a larger number of patients, so that the conclusions are more representative.

20.
Antibodies (Basel) ; 11(4)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2109902

ABSTRACT

INTRODUCTION: We documented the total spike antibody (S-Ab), IgG S-Ab and neutralizing antibody (N-Ab) responses of BNT162b2/CoronaVac vaccinees up to 90 days post-booster dose. METHODS: We included 32 homologous regimen CoronaVac vaccinees and 136 BNT162b2 mRNA vaccinees. We tested their total S-Ab (Roche), IgG (Abbott) and N-Ab (Snibe) levels at set time points from January 2021 to April 2022. All subjects were deemed to be COVID-19-naïve either via clinical history (CoronaVac vaccinees) or nucleocapsid antibody testing (BNT162b2 vaccinees). RESULTS: All antibodies peaked 20-30 days post-inoculation. In BNT162b2 vaccinees, all post-booster antibodies were significantly higher than second-dose peaks. In CoronaVac vaccinees, IgG showed no significant differences between peak third-/second-dose titers (difference of 56.0 BAU/mL, 95% CI of -17.1 to 129, p = 0.0894). The post-vaccination titers of all antibodies in BNT162b2 vaccinees were significantly higher than those in CoronaVac vaccinees at all time points. Post-booster, all antibodies declined in 90 days; the final total/IgG/N-Ab titers were 7536 BAU/mL, 1276 BAU/mL and 12.5 µg/mL in BNT162b2 vaccinees and 646 BAU/mL, 62.4 BAU/mL and 0.44 µg/mL in CoronaVac vaccinees. CONCLUSION: The mRNA vaccine generated more robust total S-Ab, IgG and N-Ab responses after the second and third vaccinations.

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