COVID-19 Therapeutic Potential of Natural Products.

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

Zika Virus Vaccine: The Current State of Affairs and Challenges Posed by Antibody-Dependent Enhancement Reaction.

Infection caused by the Zika virus (ZIKV) can lead to serious neurological complications such as microcephaly in neonates. At present, no approved ZIKV vaccine is available, but few vaccine candidates are undergoing clinical trial. One major challenge faced is antibody-dependent enhancement (ADE) reaction that may provoke severe outcome in subsequent infection by ZIKV or other flaviviruses. Thus, more efforts should be dedicated to understanding ADE in designing a safe and effective vaccine to minimize the consequence of the potentially fatal infection's complications and to tackle potential ZIKV reemergence. This review discusses different types of ZIKV vaccine candidates that are currently underway in various stages of preclinical and clinical evaluations.

MERS-CoV seroconversion amongst Malaysian Hajj pilgrims returning from the Middle East, 2016-2018: results from the MERCURIAL multiyear prospective cohort study.

Prospective cohort study to investigate the potential exposure to the Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) following Hajj pilgrims is still very limited. Here, we report the antibody seroconversion study results obtained from successive three years cohort studies (2016-2018) involving the Malaysian Hajj pilgrims returning from the Middle East. A cohort study of Hajj pilgrims from Malaysia enrolled 2,863 participants from 2016-2018, all of whom consented to provide paired blood samples for both pre- and post-Hajj travel to the Middle East. ELISAs and micro-neutralization assays were performed to detect the presence of MERS-CoV IgG antibodies. Sociodemographic data, symptoms experienced during Hajj, and history of exposure to camels or camel products were recorded using structured pre- and post-Hajj questionnaires. A 4-fold increase in anti-MERS-CoV IgG between paired pre-Hajj and post-Hajj serum samples in twelve participants was observed. None of the twelve ELISA-positive sera had detectable levels of virus-neutralizing antibodies. All reportedly had mild symptoms of respiratory symptoms at a certain point during the pilgrimage, implying mild or asymptomatic infections. No association between post-Hajj serum positivity and a history of exposure to camels or camel products was obtained. Findings from the study suggest that serologic conversion to MERS-CoV occurred in at least 0.6% of the Hajj pilgrims returning from the Middle East. Since all the seroconvertants had mild to no symptoms during the sampling period, it highlights the likelihood of occurrence of only low infectivity spillover infections among the Hajj pilgrims.

The clinical utility of CD163 in viral diseases.

Macrophage activation and hypercytokinemia are notable presentations in certain viral infections leading to severe disease and poor prognosis. Viral infections can cause macrophage polarization into the pro-inflammatory M1 or anti-inflammatory M2 phenotype. Activated M1 macrophages usually restrict viral replication whereas activated M2 macrophages suppress inflammation and promote tissue repair. In response to inflammatory stimuli, macrophages polarize to the M2 phenotype expressing hemoglobin scavenger CD163 surface receptor. The CD163 receptor is shed as the soluble form, sCD163, into plasma or tissue fluids. sCD163 causes detoxification of pro-oxidative hemoglobin which produces anti-inflammatory metabolites that promote the resolution of inflammation. Hence, increased CD163 expression in tissues and elevated circulatory levels of sCD163 have been associated with acute and chronic inflammatory diseases. CD163 and other macrophage activation markers have been commonly included in the investigation of disease pathogenesis and progression. This review provides an overview of the involvement of CD163 in viral diseases. The clinical utility of CD163 in viral disease diagnosis, progression, prognosis and treatment evaluation is discussed.

Exploring NFκB pathway as a potent strategy to mitigate COVID-19 severe morbidity and mortality.

The pandemic of coronavirus disease 2019 (COVID-19), for which there does not appear to be an approved cure, the primary treatment options consist of non-pharmacological preventive measures and supportive treatment that are aimed at halting the progression of the disease. Nuclear factor kappa B (NFkB) presents a promising therapeutic opportunity to mitigate COVID-19-induced cytokine storm and reduce the risk of severe morbidity and mortality resulting from the disease. However, the effective clinical application of NFkB modulators in COVID-19 is hampered by a number of factors that must be taken into consideration. This paper therefore explored the modulation of the NFB pathway as a potential strategy to mitigate the severe morbidity and mortality caused by COVID-19. The paper also discusses the factors that form the barrier, and it offers potential solutions to the various limitations that may impede the clinical use of NFkB modulators against COVID-19. This paper revealed and identified three key potential solutions for the future clinical use of NFkB modulators against COVID-19. These solutions are pulmonary tissue-specific NFkB blockade, agents that target common regulatory proteins of both canonical and non-canonical NFkB pathways, and monitoring clinical indicators of hyperinflammation and cytokine storm in COVID-19 prior to using NFkB modulators.

SARS-CoV-2 genomic surveillance in Malaysia: displacement of B.1.617.2 with AY lineages as the dominant Delta variants and the introduction of Omicron during the fourth epidemic wave.

OBJECTIVES: This study reported SARS-CoV-2 whole genome sequencing results from June 2021 to January 2022 from seven genome sequencing centers in Malaysia as part of the national surveillance program. METHODS: COVID-19 samples that tested positive by reverse transcription polymerase chain reaction and with cycle threshold values <30 were obtained throughout Malaysia. Sequencing of SARS-CoV-2 complete genomes was performed using Illumina, Oxford Nanopore, or Ion Torrent platforms. A total of 6163 SARS-CoV-2 complete genome sequences were generated over the surveillance period. All sequences were submitted to the Global Initiative on Sharing All Influenza Data database. RESULTS: From June 2021 to January 2022, Malaysia experienced the fourth wave of COVID-19 dominated by the Delta variant of concern, including the original B.1.617.2 lineage and descendant AY lineages. The B.1.617.2 lineage was identified as the early dominant circulating strain throughout the country but over time, was displaced by AY.59 and AY.79 lineages in Peninsular (west) Malaysia, and the AY.23 lineage in east Malaysia. In December 2021, pilgrims returning from Saudi Arabia facilitated the introduction and spread of the BA.1 lineage (Omicron variant of concern) in the country. CONCLUSION: The changing trends of circulating SARS-CoV-2 lineages were identified, with differences observed between west and east Malaysia. This initiative highlighted the importance of leveraging research expertise in the country to facilitate pandemic response and preparedness.

Malaysian Parents' Willingness to Vaccinate Their Children against COVID-19 Infection and Their Perception of mRNA COVID-19 Vaccines.

Little was known about Malaysian parental attitudes, beliefs, and intentions surrounding coronavirus disease 2019 (COVID-19) vaccines for children when the National COVID-19 Immunization Program for Children (PICKids) was launched in February 2021. A cross-sectional online survey-based study was carried out from 15 March 2022 to 23 July 2022 on Malaysian parents/guardians of children between ages 5 and below 12 years old. A total of 15.7% reported being extremely willing, and 38.9% were somewhat willing to vaccinate children with a COVID-19 vaccine. Perceived low susceptibility to COVID-19 infection showed the greatest significant impact on vaccine acceptance (OR 35.46, 95% CI 15.26-82.40). Parents with a lower level of concern have a higher willingness for vaccination (OR 1.25, 95% CI 0.90-1.75). Of the parents that knew of the mRNA vaccine, 46.6% reported that they prefer their children to be vaccinated with conventional vaccines over mRNA vaccines. Poor knowledge about mRNA vaccines, lack of confidence in the mRNA technology, fear of unknown side effects, and perception that the mRNA vaccines contain microchips were significantly associated with a higher level of concern about their children receiving an mRNA vaccine. Public education campaigns to promote COVID-19 vaccination for children warrant addressing the concerns and knowledge deficits among vaccine-hesitant parents.

Knowledge of SARS-CoV-2 Epitopes and Population HLA Types Is Important in the Design of COVID-19 Vaccines.

The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization's Emergency Use Listing. Notwithstanding the diverse worldwide population genetics, the vaccines thus far developed are generic in nature for use worldwide. Differences in the human leukocyte antigen (HLA) in different populations, variation of the T cell epitopes, and the propensity of SARS-CoV-2 genetic mutations left room for improvement of the vaccines. Here, we discussed the implications of COVID-19 vaccination and SARS-CoV-2 infection by taking into consideration SARS-CoV-2 mutations, T cell epitopes, risk factors, and current platforms of candidate vaccines based on the HLA types that are commonly present in Peninsular Malaysia Chinese, Indian, and Malay populations. The HLA types associated with protection against and susceptibility to severe SARS-CoV-2 infection were identified based on reported case-control and cohort studies. The relevance of including the non-spike SARS-CoV-2 proteins in the future COVID-19 vaccines is also highlighted. This review is meant to trigger researchers to acknowledge the importance of investigating the possible relationships between the HLA haplotype and the SARS-CoV-2 strains circulating in different populations.

Acceptability for COVID-19 vaccination: perspectives from Muslims.

This study aims to assess COVID-19 vaccine acceptance among Muslims in Malaysia. A cross-sectional internet-based survey was to determine acceptance of COVID-19 vaccine. Other influential factors, namely socio-demographics, COVID-19 experience, self-perceived level of religiosity, support in immunization, COVID-19 immunization attitudes, and health fatalistic beliefs (measured using the Helpless Inevitability Subscale of the Religious Health Fatalism Questionnaire, RHFQ-HI) were investigated. The majority reported a definite intent to receive the COVID-19 vaccine (57.3%; 95% CI 55.0-59.6) followed by a probable intent (42.7%; 95% CI 40.4-45.0%). COVID-19 immunization attitudes measured by attitudinal barriers to vaccination scores were found to be the strongest influence of COVID-19 vaccination intent, whereby participants who have lower attitudinal barrier scores reported higher COVID-19 vaccination intent (OR = 6.75 ; 95% 5.20-8.75). Although religious health fatalism was not significantly associated with vaccination intent, a significantly higher proportion of participants with score 4-9 (61.9%) in the RHFQ-HI reported intent to receive COVID-19 vaccine than those with a score of 10-20 (53.5%), p < .001. Intervention for people with skeptical attitudes toward COVID-19 vaccination is warranted.

The Pandemic Experience in Southeast Asia: Interface Between SARS-CoV-2, Malaria, and Dengue.

Southeast Asia (SEA) emerged relatively unscathed from the first year of the global SARS-CoV-2 pandemic, but as of July 2021 the region is experiencing a surge in case numbers primarily driven by Alpha (B.1.1.7) and subsequently the more transmissible Delta (B.1.617.2) variants. While initial disease burden was mitigated by swift government responses, favorable cultural and societal factors, the more recent rise in cases suggests an under-appreciation of prior prevalence and over-appreciation of possible cross-protective immunity from exposure to endemic viruses, and highlights the effects of vaccine rollout at varying tempos and of variable efficacy. This burgeoning crisis is further complicated by co-existence of malaria and dengue in the region, with implications of serological cross-reactivity on interpretation of SARS-CoV-2 assays and competing resource demands impacting efforts to contain both endemic and pandemic disease.

Emergence of B.1.524(G) SARS-CoV-2 in Malaysia during the third COVID-19 epidemic wave.

The COVID-19 pandemic first emerged in Malaysia in Jan 2020. As of 12th Sept 2021, 1,979,698 COVID-19 cases that occurred over three major epidemic waves were confirmed. The virus contributing to the three epidemic waves has not been well-studied. We sequenced the genome of 22 SARS-CoV-2 strains detected in Malaysia during the second and the ongoing third wave of the COVID-19 epidemic. Detailed phylogenetic and genetic variation analyses of the SARS-CoV-2 isolate genomes were performed using these newly determined sequences and all other available sequences. Results from the analyses suggested multiple independent introductions of SARS-CoV-2 into Malaysia. A new B.1.524(G) lineage with S-D614G mutation was detected in Sabah, East Malaysia and Selangor, Peninsular Malaysia on 7th October 2020 and 14th October 2020, respectively. This new B.1.524(G) group was not the direct descendant of any of the previously detected lineages. The new B.1.524(G) carried a set of genetic variations, including A701V (position variant frequency = 0.0007) in Spike protein and a novel G114T mutation at the 5'UTR. The biological importance of the specific mutations remained unknown. The sequential appearance of the mutations, however, suggests that the spread of the new B.1.524(G) lineages likely begun in Sabah and then spread to Selangor. The findings presented here support the importance of SARS-CoV-2 full genome sequencing as a tool to establish an epidemiological link between cases or clusters of COVID-19 worldwide.

Assessment of Impact of Containment During the COVID-19 Epidemic and Coping Behaviours Using Newly Developed Assessment Tools

Background: The confinement measures during COVID-19 had a massive effect on physical and psychological health in public. This study assessed the impact of containment and coping behaviour among the Malaysia public during the COVID-19 pandemic. Questions assessing the impact of containment and coping behaviours were developed and psychometrically tested. Methods: Exploratory factor analysis (EFA) was conducted with the items using principal component analysis extraction and Varimax rotation. Partial least squares structural equation modelling was used to determine the relationship between coping and impact. Results: The 13-item of impact and 10-item coping instruments were developed with three dimensions identified through EFA. Both scales demonstrated excellent composite reliability and good convergent validity. The survey findings revealed that the impact on individual psychological aspects was prominent, followed by well-being and lifestyle. Mindfulness and physical coping strategies were most commonly reported. Coping through seeking help from health professionals and hotlines had a positive direct effect on well-being and lifestyle (b = 0.231, p < 0.001), psychological (B = 0.132, p < 0.001), and employment-related (0.194, p < 0.001) impacts. Coping through mindfulness practise had a negative effect on well-being and lifestyle-related impact (B = −0.180, p < 0.001) and employment-related impact (B = −0.096, p = 0.008). Conclusions: Despite some limitation, the scales for measuring impact and coping behaviours have the potential to be used as a measurement tool in future studies. Findings highlight the enormous impact of the pandemic on psychological well-being and lifestyles. Health authorities should support individual coping as it was found to be an important resilience-related factor to mitigate the impacts of containment during the pandemic.

Baicalein and Baicalin Inhibit SARS-CoV-2 RNA-Dependent-RNA Polymerase.

Coronavirus Disease 2019 (COVID-19) is a deadly emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is easily transmitted through the air and has a relatively long incubation time, COVID-19 has rapidly developed into a global pandemic. As there are no antiviral agents for the prevention and treatment of this severe pathogen except for remdesivir, development of antiviral therapies to treat infected individuals remains highly urgent. Here, we showed that baicalein and baicalin exhibited significant antiviral activity against SARS-CoV-2, the causative agent of COVID-19 through in vitro studies. Our data through cell-based and biochemical studies showed that both compounds act as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors directly and inhibit the activity of the SARS-CoV-2 RdRp, but baicalein was more potent. We also showed specific binding of baicalein to the SARS-CoV-2 RdRp, making it a potential candidate for further studies towards therapeutic development for COVID-19 as a selective non-nucleoside polymerase inhibitor.

In vitro virucidal activity of povidone iodine gargle and mouthwash against SARS-CoV-2: implications for dental practice.

Introduction Virus particles in respiratory droplets and aerosols generated during medical/dental procedures are a potential source of SARS-CoV-2 cross infection. In the dental setting, oral decontamination could be an important adjunct to personal protective equipment and is recommended by a number of national COVID-19 guidance documents for dental settings.Aim To assess the in vitrovirucidal activity of an oral povidone iodine (PVP-I) product against SARS-CoV-2.Material and methods BETADINE gargle and mouthwash (1% PVP-I) was tested against SARS-CoV-2 virus under both clean and dirty conditions using a suspension assay based on EN14476 methodology. Virucidal activity of the product, undiluted and at 1:2 dilution, was tested at contact times of 15, 30 and 60 seconds. Viral titres were calculated using the Spearman-Kärber method and reported as median tissue culture infectious dose (TCID50/ml).Results The undiluted product achieved >5 log10 reduction in viral titres compared to the control at 15, 30 and 60 seconds under both clean and dirty conditions. At a twofold dilution (0.5% PVP-I), the test product demonstrated >4 log10 kill at 15 seconds and >5 log10 kill at 30 and 60 seconds in both clean and dirty conditions.Conclusion PVP-I gargle and mouthwash product, undiluted and at 1:2 dilution, demonstrated potent and rapid virucidal activity (≥4 log10 reduction of viral titre) in 15 seconds against SARS-CoV-2 in vitro. The PVP-I gargle and mouthwash product is widely available and could be readily integrated into infection control measures during dental treatment including pre-procedural oral decontamination.

The use of the health belief model to assess predictors of intent to receive the COVID-19 vaccine and willingness to pay.

BACKGROUND: The development of a vaccine against SARS-CoV-2 infection is on the way. To prepare for public availability, the acceptability of a hypothetical COVID-19 vaccine and willingness to pay (WTP) were assessed to provide insights into future demand forecasts and pricing considerations. METHODS: A cross-sectional survey was conducted from 3 to 12 April 2020. The health belief model (HBM) was used to assess predictors of the intent to receive the vaccine and the WTP. RESULTS: A total of 1,159 complete responses was received. The majority reported a definite intent to receive the vaccine (48.2%), followed by a probable intent (29.8%) and a possible intent (16.3%). Both items under the perceived benefits construct in the HBM, namely believe the vaccination decreases the chance of infection (OR = 2.51, 95% CI 1.19-5.26) and the vaccination makes them feel less worry (OR = 2.19, 95% CI 1.03-4.65), were found to have the highest significant odds of a definite intention to take the vaccine. The mean ± standard deviation (SD) for the amount that participants were willing to pay for a dose of COVID-19 vaccine was MYR$134.0 (SD±79.2) [US$30.66 ± 18.12]. Most of the participants were willing to pay an amount of MYR$100 [US$23] (28.9%) and MYR$50 [US$11.5] (27.2%) for the vaccine. The higher marginal WTP for the vaccine was influenced by no affordability barriers as well as by socio-economic factors, such as higher education levels, professional and managerial occupations and higher incomes. CONCLUSIONS: The findings demonstrate the utility of HBM constructs in understanding COVID-19 vaccination intention and WTP.