Research - The latest Publications

Human cytokeratin 1 plays a role in the interaction of Pteropine orthoreovirus with Hek293 cells but not HeLa cells

Pteropine orthoreovirus (PRV) causes respiratory tract infections in humans. Despite its emergence as a zoonotic and respiratory virus, little is known about its cell tropism, which hampers progress in fully understanding its pathogenesis in humans. Hek293 cells are most susceptible to PRV infection, while HeLa cells are the least. Human cytokeratin 1 (CK1) was identified as the protein that interacts with PRV. The immunofluorescence assay and qPCR results revealed prior treatment with anti-CK1 may provide Hek293 cells protection against PRV. The KRT1-knockout Hek293 cells were less susceptible to PRV infection. Further study into the pathogenesis of PRV in humans is needed.

TB or not TB: emerging mycobacteriaceae detected in a human patient, tree shrews, and soil

This study investigated the extrapulmonary pathogenesis of a novel Mycobacteroides abscessus subsp. massiliense strain in a young adult, manifesting as a chronic cutaneous infection. Epidemiological investigation proposed pathogen transmission via contaminated Java apple fruit, likely facilitated by tree shrews. The strain, identified through next-generation sequencing, demonstrated resistance to 76.7% of tested antibiotics, and potential heteroresistance among the M. abscessus subsp. massiliense subpopulations were suggested. Mycobacteroides abscessus complex (MAC) is a group of non-tuberculous mycobacteria, typically associated with soil and water, and poses significant clinical challenges due to its resistance to conventional treatments and its similarity to Mycobacterium tuberculosis. The findings underscore the necessity for further genetic studies to confirm heteroresistant subpopulations and address the complexities of MAC infections.

Bat coronavirus was detected positive from insectivorous bats in Krau Wildlife Reserve Forest

Bats are flying mammals with unique immune systems that allow them to hold many pathogens. Hence, they are recognised as the reservoir of many zoonotic pathogens. In this study, we performed molecular detection to detect coronaviruses, paramyxoviruses, pteropine orthoreoviruses and dengue viruses from samples collected from insectivorous bats in Krau Reserve Forest. One faecal sample from Rhinolophus spp. was detected positive for coronavirus. Based on BLASTN, phylogenetic analysis and pairwise alignment-based sequence identity calculation, the detected bat coronavirus is most likely to be a bat betacoronavirus lineage slightly different from coronavirus from China, Philippines, Thailand and Luxembourg. In summary, continuous surveillance of bat virome should be encouraged, as Krau Reserve Forest reported a wide spectrum of biodiversity of insectivorous and fruit bats. Moreover, the usage of primers for the broad detection of viruses should be reconsidered because geographical variations might affect the sensitivity of primers in a molecular approach.

Oncolytic Reoviruses: Can These Emerging Zoonotic Reoviruses Be Tamed and Utilized?

Orthoreovirus is a nonenveloped double-stranded RNA virus under the Reoviridae family. This group of viruses, especially mammalian orthoreovirus (MRV), are reported with great therapeutic values due to their oncolytic effects. In this review, the life cycle and oncolytic effect of MRV and a few emerging reoviruses were summarized. This article also highlights the challenges and strategies of utilizing MRV and the emerging reoviruses, avian orthoreovirus (ARV) and pteropine orthoreovirus (PRV), as oncolytic viruses (OVs). Besides, the emergence of potential ARV and PRV as OVs were discussed in comparison to MRV. Finally, the risk of reovirus as zoonosis or reverse zoonosis (zooanthroponosis) was debated, and concerns were raised in this article, which warrants continued surveillance of reovirus (MRV, ARV, and PRV) in animals, humans, and the environment.

Fighting nature with nature: antiviral compounds that target retroviruses

The human immunodeficiency virus (HIV) is a type of lentivirus that targets the human immune system and leads to acquired immunodeficiency syndrome (AIDS) at a later stage. Up to 2021, there are millions still living with HIV and many have lost their lives. To date, many anti-HIV compounds have been discovered in living organisms, especially plants and marine sponges. However, no treatment can offer a complete cure, but only suppressing it with a life-long medication, known as combined antiretroviral therapy (cART) or highly active antiretroviral therapy (HAART) which are often associated with various adverse effects. Also, it takes many years for a discovered compound to be approved for clinical use. Thus, employing advanced technologies such as automation, conducting systematic screening and testing protocols may boost the discovery and development of potent and curative therapeutics for HIV infection/AIDS. In this review, we aim to summarize the antiretroviral therapies/compounds and their associated drawbacks since the discovery of azidothymidine. Additionally, we aim to provide an updated analysis of the most recent discoveries of promising antiretroviral candidates, along with an exploration of the current limitations within antiretroviral research. Finally, we intend to glean insightful perspectives and propose future research directions in this crucial area of study.

House dust mites eradication treatments: Current updates emphasizing on tropical countries

House Dust Mites (HDMs) like Dermatophagoides farinae (D. farinae), Dermatophagoides pteronyssinus (D. pteronyssinus) and Blomia tropicalis (B. tropicalis) were found all over the world. Their relationship with allergy diseases was one of the focal points of epidemiological investigations spanning various geographical regions globally but specifically in regions with warm temperatures. Their omnipresence underscores their pivotal role in the etiology and exacerbation of some respiratory disorders, emphasizing their significance as environmental allergens. Despite the availability of numerous eradication treatments ranging from sun exposure to ozone-based approaches, the quest for efficacious HDM eradication encounters obstacles due to the diversity in study methodologies employed to evaluate these different intervention strategies. This methodological heterogeneity complicates the quantification of treatment efficacy, impeding the establishment of definitive criteria distinguishing "effective" from "ineffective" approaches. Despite the urgency of developing solutions, current efforts are hindered by this lack of consensus. This review aims to bridge this gap by synthesizing existing knowledge on HDM eradication strategies and discussing their efficacy, safety, and practicality. By addressing these discrepancies, this article endeavors to provide insights and clues for the future development of evidence-based interventions aimed at mitigating HDM infestations and ultimately reducing its sensitization rate worldwide.

Pteropine Orthoreovirus (PRV7S) does not Establish Persistent Infection in NP460 Cells but with Inflammatory Response Triggered

Seroprevalence of Pteropine orthoreovirus and Mammalian orthoreovirus among swine (porcine) in Peninsular Malaysia.

Aims: To determine the seroprevalence of Mammalian orthoreovirus (MRV) and different Pteropine orthoreovirus (PRV) members using swine sera from different regions of Peninsular Malaysia. Methodology and results: A total of 60 blood specimens were collected. Twenty specimens (10 sows + 10 weaners/region) were collected from the Northern (Penang and Perak), Southern (Johor) and Central (Selangor and Malacca/Melaka) regions of Peninsular Malaysia. Then, a serum virus neutralization assay was performed against MRV3, Nelson Bay virus (PRV1NB), Pulau virus (PRV2P), Melaka virus (PRV3M), Kampar virus (PRV4K) and Sikamat virus (PRV7S). MRV3 alone contributed to 48.1% (n=13) of the seropositive samples, while the PRVs accounted for 51.9% (n=14) of seropositive samples. Among the PRVs, PRV4K (n=5, 8.3%) was the most prevalent, followed by PRV7S (n=4, 6.7%), PRV2P (n=3, 5%) and PRV3M (n=2, 3.3%). Approximately 33.3% (n=20) of the swine were seropositive for at least 1 reovirus. Both the sows (n=13, 21.7%) and weaners (n=14, 23.3%) have a similar risk of being seropositive for at least 1 reovirus. Conclusion, significance and impact of study: Both MRV3 and PRVs are equally prevalent among swine in Peninsular Malaysia. Despite their low pathogenicity and the fact that they are not deadly to humans, MRV can increase mortality rates and cause neurological problems in pigs. However, no MRV or PRV vaccines are currently available in Malaysia. Further research is needed to assess whether it is necessary and worthwhile to invest in the development of MRV and PRV vaccines.

Human Adenovirus Respiratory Infection among Hospitalized Children in Seremban, Malaysia (Preprint)

This study aims to isolate clinical adenovirus among hospitalized children in Seremban, Malaysia. After that, determination of the serotype and genetic relatedness of isolated adenovirus through phylogenetic analysis with the published database of human adenovirus from GenBank will be carried out. 26 HAdV-positive retrospective respiratory specimens were collected from pediatric patients with respiratory distress at the Pediatric Department of Hospital Tuanku Jaafar in Seremban, Malaysia. HAdV was isolated in A549 cell culture, sequenced and analysed for HAdV typing. Based on hexon, penton, DNA polymerase, fiber, and virus-associated (VA) RNAII genes, there were 22/26 samples (84.62%) and 3/26 samples (11.54%) belonging to serotypes 7 and 3, respectively. Also, 1/26 sample (3.85%) was determined as HAdV subgroup D. In short, this study serves as a continuation to monitor the prevalence of HAdV serotypes in Malaysia and our result shows HAdV B as the most predominant circulating group of HAdV in Malaysia between 2013 – 2017.

Redefining Vaccines: Nucleic Acid Vaccines Encoding Short Therapeutic Peptides (Preprint)

Nucleic acids not only serve as the blueprint of living things, but are also involved in biological processes within an organism. A peptide is a short chain of amino acids encoded in a gene. Both nucleic acids (1990) and peptides (first use of insulin in 1922) were developed and used for therapeutic purposes beginning in the last century. Nucleic acid- and peptide-based vaccines are two classic types of vaccines used to immunize and protect us from many infectious and noncommunicable diseases. Among them, microRNAs, short-interfering RNAs, and antimicrobial peptides/therapeutic peptides are some of the well-established therapeutic vaccines. Recently, a study by Siew et al. (2024) suggested that cyclotide is a suitable candidate for the development of an mRNA-cyclotide vaccine. It was proposed that this technology may improve the overall efficacy and potency of cyclotide as an antiretroviral peptide. Cyclotides are a group of peptides with a head-to-tail cyclized backbone that can be found mainly in plants. They are reported to have a wide range of biological activities. Hence, in this article, we theoretically discuss the proposed mRNA-cyclotide vaccine with further insight into antiretroviral cyclotides. The proposed mRNA-cyclotide vaccine was also compared to two classical vaccines.