Research

• COVID19

Several members of the family Coronaviridae constantly circulate in the human population and usually cause mild respiratory disease. In contrast, the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) are transmitted from animals to humans and cause severe respiratory diseases in afflicted individuals, SARS and MERS, respectively. The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. However, no drug or vaccine has yet been approved to treat human coronaviruses. Several options can be attempted to control or prevent emerging infections of 2019-nCoV, including vaccines, monoclonal antibodies, oligonucleotide-based therapies, peptides, interferon therapies and small-molecule drugs. Given the urgency of the 2019-nCoV outbreak, we focus on the development potential anti-SARS-CoV-2 drug through repurposition of existing approved drug and target based drug development.

• Hepatitis B Virus (HBV)

Chronic hepatitis B virus (HBV) infection is a common cause of liver disease. Vaccines and nucleoside or nucleotide drugs are available and reduce new infection rates. However, HBV positive patients are required to take currently approved anti-HBV drugs for life. Recently, many researchers have recognized the importance of addressing the persistence of episomal covalently closed circular DNA, the existence of integrated HBV DNA in the host genome and the large antigen load, particularly of hepatitis B surface antigen. Another major challenge is to reinvigorate the exhausted immune response within the liver microenvironment. Based on this background, we are currently working on the development of antiviral drugs against hepatitis B virus.

• Picornavirus

Picornaviridae, a group of positive-strand RNA viruses that includes many important human pathogens. Within the Picornaviridae, there are four human enterovirus (HEV) species, called HEV-A to HEV-D, which in total comprise more than 100 virus (sero)types. Well-known members of the HEV-A species are the coxsackie A viruses and the emerging neurotropic enterovirus 71 (EV71). These viruses are the major ethological agents of hand-foot-and-mouth disease, especially in young children. EV71 can also cause severe neurological diseases, including brain stem encephalitis and poliomyelitis-like paralysis. The HEV-B species comprise the coxsackie B viruses and echoviruses, which are the main causes of viral meningitis, myocarditis, and pancreatitis. Coxsackieviruses are also associated with type 1 diabetes. The most extensively studied enterovirus is poliovirus (PV), which belongs to the HEV-C species and is the causative agent of paralytic poliomyelitis. The HEV-D species contains five viruses, including EV68 and EV70, which can cause clinical symptoms ranging from hand-foot-and-mouth disease to respiratory tract infections and acute hemorrhagic conjunctivitis.

The three species of human rhinoviruses (HRV), HRV-A to HRV-C, are also classified within the Enterovirus genus and all together contain 150 serotypes. HRV is the main cause of the common cold, which poses a significant socioeconomic burden, with millions of days of absence from work or school, and often leads to improper use of antibiotics. 

There are two strategies to combat viral infections: the use of vaccines to prevent disease, or drugs to inhibit viral replication. For picornaviruses, a vaccine is only available for PV, while EV71 vaccine candidates are currently being evaluated in clinical trials. The development of vaccines against other nonpolio picornaviruses seems essentially impossible, given the large variety of (sero)types. Hence, antiviral drugs are urgently needed for the prophylaxis and/or treatment of picornavirus infections.

• Influenza

Influenza virus infection can be prevented by vaccination and therapeutic treatment available with viral neuraminidase (NA) or matrix protein (M2) inhibitors. Nevertheless, it has not been eradicated and has become a major cause of seasonally regional or pandemic threat to humans. Its ability to shelter in various mammals or birds and to persistently evolve via antigenic drift or shift results in generation of uncharacterized viruses. It is also believed that they might have resistance developed to available treatments. Clinically, a series of adamantanes (M2 inhibitors) are available for the treatment of influenza type A viruses, but are ineffective against type B virus or M2-mutant viruses of H1N1 and H3N2. Also the side effects associated with them in the central nervous system are severe. Well known NA inhibitors have broad-spectrum activity against various (sub) types of influenza viruses. Although oseltamivir phosphate (OSV-P) is safe compared with the adamantanes but increasing frequency of oseltamivirresistant mutants and their cross-resistance to another NA inhibitor, e.g., zanamivir, provoke the need for development of alternative antiviral drugs with different modes-of-action. Thus, the discovery of novel anti-influenza agents is urgently needed.

• Antibacterial Drug Discovery

Global antibiotic resistance has reached critically urgent levels, as expected in the AMR (antimicrobial resistance) reports, warning that it could cause 10 million annual deaths by 2050 in the absence of actions to tackle AMR. 

Deaths attributable to AMR in 2050 compared to other major causes of mortality