The antiviral effect of jiadifenoic acids C against coxsackievirus B3

Abstract

Coxsackievirus B type 3 (CVB3) is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM) and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs). The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.

Purification of Houttuynia cordata Thunb. Essential Oil Using Macroporous Resin Followed by Microemulsion Encapsulation to Improve Its Safety and Antiviral Activity

“…The in vitro antiviral activities of HEHEO, crude HEO, pure HEO, and HME against CVB3 and B6 were evaluated by using the conventional CPE method [ 37 ]. As shown in Table 6 , HEHEO exhibited weak activity against CVB3 with IC 50 of 17.24 µg/mL.…”

Research Progress in the Pharmacological Activities, Toxicities, and Pharmacokinetics of Sophoridine and Its Derivatives

“… 49 Although the pathogenesis of CVB3 has been studied extensively in mouse models and a lot of work has been done on the development of vaccines and therapeutic agents against CVB3, no effective clinical therapeutic methods have been established so far. 50 , 51 Per Zhang et al (2006) sophoridine exhibited antiviral properties against CVB3 both in vitro (primary myocardial cells) and in vivo (BALB/c mice) by speeding up IL-10 and IFN-γ production and shrinking TNF-α levels, possibly through locatine itself rather than via a metabolite. 52 …”

Novel N-Benzenesulfonyl Sophocarpinol Derivatives as Coxsackie B Virus Inhibitors

“…9−11 However, there has been no special efficient drug approved for the treatment of the infections caused by CVB3 until now. 12 Therefore, there is an urgent need to develop broad-spectrum antiviral candidates against enteroviruses to meet an emergency of sudden infectious diseases. (1); E-β,γ-sophocarpinic acid (2); E-β,γ-12-N-m-cyanobenzene-sulfonyl sophocarpinic acid (3); E-β,γ-12-N-p-trifluoromethy-benzenesulfonyl sophocarpinic acid (4); and Z-α,β-sophocarpinic acid (14).…”

“…9−11 However, there has been no special efficient drug approved for the treatment of the infections caused by CVB3 until now. 12 Therefore, there is an urgent need to develop broad-spectrum antiviral candidates against enteroviruses to meet an emergency of sudden infectious diseases. Sophocarpine (1, Figure 1), a natural medicine extracted from Chinese herb Sophora f lavescens, has been used to treat viral myocarditis caused by CVB3 for decades in China with an unknown mechanism of action.…”

“…Enteroviruses are a genus of single-stranded (+) RNA viruses associated with many human diseases. , Among the enteroviruses, coxsackie B viruses (CVB) are important human pathogens causing pleurodynia, myocarditis, hepatitis, and so on. , Coxsackievirus type B3 (CVB3) is an important pathogen that induces acute and chronic viral myocarditis in children and young adults, and eventually leads to cardiomyopathy. , Besides heart infections, CVB3 causes chronic inflammatory diseases of the pancreas and central nervous system as well. , In recent years, the sudden epidemic infections of enteroviruses have caused great concerns of society. − However, there has been no special efficient drug approved for the treatment of the infections caused by CVB3 until now . Therefore, there is an urgent need to develop broad-spectrum antiviral candidates against enteroviruses to meet an emergency of sudden infectious diseases.…”