Cannabis as antivirals.

Cannabis is a plant notorious for its psychoactive effect, but when used correctly, it provides a plethora of medicinal benefits. With more than 400 active compounds that have therapeutic properties, cannabis has been accepted widely as a medical treatment and for recreational purposes in several countries. The compounds exhibit various clinical benefits, which include, but are not limited to, anticancer, antimicrobial, and antioxidant properties. Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication. Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.

Deregulation of the Host Cell Cycle Induced by SARS‐CoV‐2 Nucleocapsid Protein

Introduction: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARSCoV2) is the causative agent responsible for the COVID-19 pandemic and has resulted in devastating impacts on global public health. The nucleocapsid (N) protein of other coronaviruses, such as SARS-CoV-1, have been previously implicated in the deregulation of the host cell cycle through interactions with cell cycle checkpoint proteins, Cyclin-Dependent Kinases (CDKs) or cyclins. In this study, we highlight the role of SARS-CoV-2 N-protein in modulating CDK expression, thereby, deregulating the host cell cycle. Methods: A549 cells were transfected with pCMV plasmids, harbouring the SARS-CoV-2 N-protein. Protein extracts of control and Nprotein transfected cells were electrophoresed on SDS-PAGE, transferred onto a nitrocellulose membrane and incubated with CDK2 and CDK4 antibodies. The blots were visualized and protein quantification was performed using ImageJ analysis. Results: Transfection of SARS-CoV-2 N resulted in differential expression of CDK2 and CDK4, which are key regulators that drive cell cycle progression through G0 or G1 phase into S phase. Notably, preliminary findings also demonstrate that N protein results in decreased CDK2 and CDK4 expression. Conclusion: The differential expression of CDKs caused by SARS-CoV-2 N-protein suggests its role in inducing cell cycle arrest at the S phase to facilitate SARS-CoV-2 replication. The results from this research may aid in future characterisation of the mechanisms for SARS-CoV-2-mediated cell cycle arrest, and contribute towards the development of novel antiviral strategies and therapies.

Studies on the Role of SARS-CoV-2 Nucleocapsid as an Interferon Antagonist

Introduction: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, has resulted in significantly disruptive global impacts. Cytokine storm syndrome (CSS) can accompany SARSCoV2 infection, and involves the excessive release of pro-inflammatory cytokines that lead to acute respiratory distress syndrome (ARDS) in infected patients. Given the correlation between ARDS and poor patient prognosis, inflammatory pathways (e.g., interferon-1 (IFN-1)) would be a target area for antiviral development. Our preliminary results have demonstrated a direct correlation between the SARS-CoV-2 nucleocapsid (N) protein and host intracellular IFN-1 pathway components IRF3 and STAT1. Methods: A549 cells were transfected with pCMV-GFP vectors expressing N protein and harvested. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western Blotting were performed. The membranes were then incubated with STAT-1, p-STAT1 and IRF3 antibodies and visualised. Protein content was quantified using ImageJ software. Results: Transfection with SARS-CoV-2 N was correlated with a decrease in intracellular IRF3 and reduced phosphorylation of STAT1, suggesting the involvement of N protein in the delayed IFN-1 response commonly observed in SARS-CoV-2 patients. These findings suggest that IRF3 and STAT1 may be part of the innate immune response affected by SARS-CoV-2 infection. Conclusion: Our results show that IRF3 and STAT1 are responsible for stimulating transcription of interferon signalling genes (ISGs). Future studies on SARS-CoV-2 N and its downstream effectors could provide further insight into the IFN-1 response during infection, and assist in future antiviral development strategies.

Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak.

Traditionally, drug discovery utilises a de novo design approach, which requires high cost and many years of drug development before it reaches the market. Novel drug development does not always account for orphan diseases, which have low demand and hence low-profit margins for drug developers. Recently, drug repositioning has gained recognition as an alternative approach that explores new avenues for pre-existing commercially approved or rejected drugs to treat diseases aside from the intended ones. Drug repositioning results in lower overall developmental expenses and risk assessments, as the efficacy and safety of the original drug have already been well accessed and approved by regulatory authorities. The greatest advantage of drug repositioning is that it breathes new life into the novel, rare, orphan, and resistant diseases, such as Cushing's syndrome, HIV infection, and pandemic outbreaks such as COVID-19. Repositioning existing drugs such as Hydroxychloroquine, Remdesivir, Ivermectin and Baricitinib shows good potential for COVID-19 treatment. This can crucially aid in resolving outbreaks in urgent times of need. This review discusses the past success in drug repositioning, the current technological advancement in the field, drug repositioning for personalised medicine and the ongoing research on newly emerging drugs under consideration for the COVID-19 treatment.

COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention.

Three major outbreaks of the coronavirus, a zoonotic virus known to cause respiratory disease, have been reported since 2002, including SARS-CoV, MERS-CoV and the most recent 2019-nCoV, or more recently known as SARS-CoV-2. Bats are known to be the primary animal reservoir for coronaviruses. However, in the past few decades, the virus has been able to mutate and adapt to infect humans, resulting in an animal-to-human species barrier jump. The emergence of a novel coronavirus poses a serious global public health threat and possibly carries the potential of causing a major pandemic outbreak in the naïve human population. The recent outbreak of COVID-19, the disease caused by SARS-CoV-2, in Wuhan, Hubei Province, China has infected over 36.5 million individuals and claimed over one million lives worldwide, as of 8 October 2020. The novel virus is rapidly spreading across China and has been transmitted to 213 other countries/territories across the globe. Researchers have reported that the virus is constantly evolving and spreading through asymptomatic carriers, further suggesting a high global health threat. To this end, current up-to-date information on the coronavirus evolution and SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies are summarized in this review.

Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak

Traditionally, drug discovery utilises a de novo design approach, which requires high cost and many years of drug development before it reaches the market. Novel drug development does not always account for orphan diseases, which have low demand and hence low-profit margins for drug developers. Recently, drug repositioning has gained recognition as an alternative approach that explores new avenues for pre-existing commercially approved or rejected drugs to treat diseases aside from the intended ones. Drug repositioning results in lower overall developmental expenses and risk assessments, as the efficacy and safety of the original drug have already been well accessed and approved by regulatory authorities. The greatest advantage of drug repositioning is that it breathes new life into the novel, rare, orphan, and resistant diseases, such as Cushing"s syndrome, HIV infection, and pandemic outbreaks such as COVID-19. Repositioning existing drugs such as Hydroxychloroquine, Remdesivir, Ivermectin and Baricitinib shows good potential for COVID-19 treatment. This can crucially aid in resolving outbreaks in urgent times of need. This review discusses the past success in drug repositioning, the current technological advancement in the field, drug repositioning for personalised medicine and the ongoing research on newly emerging drugs under consideration for the COVID-19 treatment.