Coronaviruses are a large group of enveloped viruses, positive sense, and have single-stranded RNA that can cause damage and infection in the respiratory tract of mammals, including humans. Coronavirus 2019 (COVID-19) is a respiratory disease initially detected in Wuhan, China in December 2019 and then spread rapidly throughout the world. This disease is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that remains in the same genus as an infectious virus in animals and humans. Genetic analysis shows that SARS-CoV-2 is closely related to bat-SL-CoVZC45 and bat-SL-CoVZXC21 as well as SARSCoV and MERS-CoV.
SARS-CoV-2 has spike proteins on the surface of the virus that binds to host receptors throughout infection. This protein has a strong affinity for human angiotensin-converting enzyme-2 (ACE2) as its receptor and is extremely efficient in infecting. After infection, SARS-CoV-2 has a polypeptide yield of approximately 800 kDa during transcription. These polypeptides have proteolytic properties that can form many proteins. This process is mediated by papain-like protease (PLpro) and 3-chymoptrypsin-like protease (3CLpro). 3CLpro is able to hydrolyze ppl and pplab viral polyproteins to produce functional proteins during coronavirus replication. These proteases play a critical role in replication and so have sequences that are essential for drug development. Therefore, 3CLpro is widely studied as a potential target inhibitor for treating SARS, MERS, and COVID-19.
Recent reports indicate several drugs that function as 3CLpro inhibitors against COVID-19 infection, namely: paxlovid and molnupiravir. Cases of COVID-19 that continue to mutate cause some of the drugs and vaccines that have been given to be less effective. Herbal plants have high potential as anti-COVID19 agents. Therefore, a therapeutic agent is required to reduce the mortality and morbidity effects of COVID-19.
Indonesia has a large diversity of plant species within the world. It is recorded that 5,000 medicinal plants have essential uses in traditional medicine since ancient times. This traditional medicine has been applied for a protracted time in Indonesia to treat viral infections such as flu, herpes, and hepatitis. According to several studies, there are significant concentrations of antiviral compounds in several plants widely studied. One of the potentials that can be used as an antiviral for SARS-CoV-2 is rhubarb (R. officinale Baill.). Rhubarb is known as a plant that is used as medicinal plants, herbal ingredients, and fragrances. In addition, emodin in rhubarb (R. officinale Baill.) has been investigated as a candidate for SARS-CoV drug. Therefore, this study aimed to determine the potential of rhubarb (R. officinale Baill.) emodin as an inhibitor of SARS-CoV-2 3CLpro activity.
The target prediction results of three compounds: emodin, paxlovid, and molnupiravir against 3CLpro showed further results. The target prediction results showed that emodin incorporates a target category in the sort of proteases as much as 6.7% of the entire target class (Figure 1). Meanwhile, the total protease target class expected with paxlovid amounted to 50%. However, the potential of molnupiravir as a predictive target is unknown. This result indicates that the potential for emodin to be targeted at proteases is little but specific, creating it appropriate to be used as a ligand substance of 3CLpro. The character of amino acid residues around the binding site is varied. The highest number of residues was found that the binding energy and stability of the secondary and the tertiary structure of the tested compound on the active site of the target enzyme.
The number of residues within the interaction of emodin with 3CLpro is sort of equivalent to the interaction between the original ligand and 3CLpro. This caused the binding affinity of the 2 ligands to be the same. Therefore, emodin has high potential as a drug candidate for inhibiting SARS-CoV-2 proteins formation. Rhubarb (R. officinale Baill.) has been tested in silico as a 3CLpro inhibitor in SARS-CoV-2. However, the results obtained by this study are theoretical and should be explored further through in vivo and in vitro tests to validate the potential advantages of the bioactive compounds present in rhubarb (R. officinale Baill.).
Rhubarb (R. officinale Baill.) was predicted to have antiviral activity because of the presence of emodin. Emodin encompasses a binding affinity value of -7.6 kcal/mol and an RMSD value of 0 so that it binds strongly to the active site of SARS-CoV-2 3CLpro. However, further research is needed to support the results of this study.
Authors: Nur Sofiatul Aini, Muhammad Hemawan Widyananda, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Alexander Patera Nugraha.
