Treatments available or under development
Since the outbreak had dealt substantial damage to the society in the whole world, lots of scientists had started to focus on seeking a viable solution to deal with the disease. Up to now, a considerable number of drugs had already under development and even started the clinical trial.
Drugs reported to be effective
Since SARS-CoV-2 belongs to the betacoronavirus, therefore, it is reasonable to use drugs used to treat SARS and MERS to inhibit the infection of the novel virus as four key enzymes in the life cycle as well as the Spike protein of the viruses are similar. Those proteins are considered promising targets for drugs.(Clercq, 2020) Whist, some other broad-spectrum antiviral drugs were also reported to be effective (Table 1).
Remdesivir, is an adenosine analogue, an antiviral drug that against a wide range of RNA viruses (includes SARS/MERS(Sheahan et al., 2017)) in both culture cells and animal models, is initially an experimental antiviral drug that treats Ebola, is now under the cooperation of Gilead Sciences Inc. with researchers and clinicians in China. It can cause the RNA chains of the viral to terminate before it gets to its mature stage and therefore fulfills its antiviral function.(Warren et al., 2016) A study by Wang et al.(M. Wang et al., 2020) had shown that Remdesivir can effectively suppress the infection of the virus in the highly sensitive human cell line (human liver cancer Huh-7 cells). From their detection, Remdesivir functions one stage after the virus entry.(M. Wang et al., 2020) The EC90 value of Remdesivir in against the SARS-CoV-2’s infection of E6 cells was 1.76μM. Whist, the EC50 value is 0·77μM(SI > 129.87).(M. Wang et al., 2020) Currently, phase III clinical trials of Remdesivir have been launched in China. In America, the first case of SARS-CoV-2 patient had been treated with Remdesivir, and now had already been cured.(Holshue et al., 2020) Also, in France, a patient was also treated with Remdesivir and also cured.(Dealmoon, 2020) But further trials are still needed as there are only a few experiments on monkey model in treating MERS but not the SARS-CoV-2.(Dealmoon, 2020)
Chloroquine, is a cheap drug with a long history that until recently been reported to have a broad-spectrum antiviral capability as well as immune-modulating activity(Savarino, Di Trani, Donatelli, Cauda, & Cassone, 2006; M. Wang et al., 2020; Yan et al., 2013). It is originally used to treat malarial and autoimmune disease and it is currently under evaluation in an open trial (ChiCTR2000029609). Chloroquine inhibits virus’s infection of the cells by escalating the endosomal PH that is essential for virus/cell fusion, and in the meanwhile, it interferes with the glycosylation of the SARS-viruses’ receptors.(Vincent et al., 2005) The result of the study by Wang et al. displayed that the drug functions at both the entry and post-entry stages of the virus invasion into the cells.(M. Wang et al., 2020) Moreover, it was reported to be widely spread in the whole body, including the lung.(M. Wang et al., 2020) The EC90value of Chloroquine in against the SARS-CoV-2’s infection of E6 cells was 6·90μM, whereas the EC50 value is 1·13μM(SI > 88·50).(M. Wang et al., 2020) So far, more than 100 patients had been used Chloroquine Phosphate to treat the disease, there have been no drug-related, obvious adverse reactions. Since it had been used for more than 70 years in treating other diseases, experts are considered it controllable and safe to enlarge the treatment to a wider population.(YSA, 2020)
Hydroxychloroquine, is a 4-aminoquinoline derivative antimalarial drug. Its action and mechanism are similar to Chloroquine, but its toxicity is only half that of Chloroquine. Medical doctors from Wuhan University People’s Hospital found that all the patients in their hospital with systemic lupus erythematosus weren’t infected with the SARS-CoV-2. Hence, they suspect that this effect may be argued by the long-termed administration of the Hydroxychloroquine to treat systemic lupus erythematosus, which helps in prevention of the infection. It seems reasonable and plausible explanation since Hydroxychloroquine has similar treating effect as Chloroquine does, and Chloroquine, as mentioned above, was reported to be effective in treatment of SARS-CoV-2. Therefore, they had treated 20 cases of the patients by using Hydroxychloroquine and found that the clinical symptoms were improved significantly in one to two days. Review of chest CT after five days of the drug use showed a significant improvement in the absorption in 19 cases. The remaining patient (previously had renal insufficiency) had progressive lesions in the chest CT, but the patient’s clinical symptoms improved significantly on the second day of Hydroxychloroquine use. In addition, none of the normal patients enrolled in the group developed severe illness, and one of them was discharged/ released on February 13.(Publish, 2020) This result had preliminary confirmed a short-term efficacy of Hydroxychloroquine in the treatment of new coronary pneumonia, which can effectively relieve symptoms, reverse the rate of exacerbation, and shorten the course of the disease. Further application trials of Hydroxychloroquine in severe and critical neo-coronary pneumonia are ongoing.
Favipiravir, is a guanine analog approved for the treatment of influenza, which effectively inhibits the RNA-dependent RNA polymerase of RNA viruses. A recent study reported its activity on SARS-CoV-2.(Clercq, 2020; M. Wang et al., 2020) A randomized trial of Favravavir in combination with interferon-α (CHICTR090029) and barbiturvir (CHICTR09009554) for SARS-CoV-2 has been conducted.(Clercq, 2020)
Besides, Chinese traditional medicine (TCM), also known as Chinese herb, was also reported to play a key role in treating the disease.(Hongzhuan, 2020) According to statistics, as of 00:00 on February 5th, the four pilot provinces used TCM to treat 214 confirmed cases had shown an over 90% rate of effective, of which the symptoms of 60% of patients experienced significant improvement, 30% of patients with stable symptoms without exacerbation.(Ping;, 2020)