On January 24th, weChat Public, “Shanghai Public Health Clinical Center”, published the “Public Health Science S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Weapons! In the face of new types of pneumonia, we are not helpless — 2019 Antiviral Treatment Options for New Coronaviruses, which describes potentially effective drugs that can be used to fight new coronaviruses.
Original title: Shanghai Public Health Clinical Center: Anti-AIDS drugs effective in the treatment of new coronary pneumonia
Source: Shanghai Public Health Clinical Center
On the same day, the author – infectious disease experts, Fudan University affiliated Shanghai Public Health Clinical Center Party Secretary Lu Hongzhou in an interview with the news, said that clinically found that some AIDS antiviral drugs used in the clinical treatment of new coronavirus pneumonia to achieve certain efficacy. From the clinical experience in Wuhan, the sooner the better, because these drugs can suppress the virus, no virus there will be some follow-up damage. Shanghai has been using this type of drug since the first patient.
Screenshot of the news video
“The Public Defender scoptics” Weapons! In the face of new types of pneumonia, we are not helpless – 2019 new coronavirus antiviral treatment options” the full text is as follows:
As of 24 hours on January 23, 2020, 29 provinces (regions and cities) in China have reported a cumulative total of 830 confirmed cases of pneumonia infection with the new coronavirus (2019-nCov), of which 177 cases of severe illness, 25 deaths, 5 cases confirmed in Hong Kong, Macao and Taiwan, and 9 cases confirmed abroad. The outbreak coincides with the Chinese Lunar New Year, and the festive atmosphere does not mask fears of its spread. “Can people be passed on”, “there is no vaccine and no special drugs” makes people feel that in the face of new viruses, modern medicine seems to have no power?
On the 23rd, Wang Guangfa, director of respiratory and critical medicine at Peking University First Hospital, who had been diagnosed with the new coronavirus, told the media that the AIDS treatment drug Lopinavir/ritonavir (Lopinavir/ritonavir, LPV/r, commodity name: Creech) was very effective for him and improved after taking it after only one day of body temperature. In fact, the National Health And Health Commission issued a pilot version of the “New Coronary Virus Infection Pneumonia Treatment Program” (now updated to the third edition), has pointed out that Creech can be used for antiviral therapy of new coronaviruses. As infectious disease specialists, in the face of the sudden outbreak of infectious diseases, we are the first-line fighters who storm into the battle, and on the battlefield we must wear masks, wear protective clothing, we have to know what weapons can be used, we are not two hands empty-handed to be pushed to the battlefield. In addition to Crech, experienced the 2003 SARS and 2012 MERS and other coronavirus infection pneumonia outbreak, we have carried out a lot of research and exploration, there are many potentially effective drugs can be used to fight the new coronavirus, here is a introduction.
In 1954, Japanese scientists discovered ‘viral interference’, a virus-infected cell, which is able to synthesize and secrete interferon, a protein that interferes with virus replication and enhances the antiviral capability of neighboring cells. Human interference is known as type I and II, type I interferon includes IFN-alpha, beta, radon, radon, etc., is produced by the synthesis of infected virus cells, type II interferon includes IFN-radon, mainly composed of T lymphocytes. At present, the main clinical antiviral therapy is IFN-alpha, which binds to the specific receptors of infected cells, thereby activating the antiviral protein gene and thus synthesizing a variety of antiviral proteins. These antiviral proteins can cut off viral nucleic acids, inhibit the synthesis of viral proteins, inhibit the assembly of viruses, and thus inhibit virus replication. IFN-alpha interferon also has a powerful immune regulation function, can activate natural killer cells, macrophages and other immune cells, enhance the host’s immune defense function. Clinically, IFN-alpha has been widely used in chronic hepatitis B, chronic hepatitis C and other diseases, but also can be used locally to improve the treatment of herpes simplex virus infection, human papillomavirus infection treatment. The pneumonia diagnosis and treatment plan for the new coronavirus infection (trial third edition) points out that IFN-alpha atomized inhalation can be used as an anti-new coronavirus treatment measure to improve the virus removal effect of the mucous membranes of the patient’s respiratory tract. In in vitro studies of MERS-CoV and Severe Acute Respiratory Syndrome (SARS-CoV), it was found that both IFN-alpha and IFN-beta inhibited the coronavirus, and in subtypes, IfN-beta 1b is best for MERS-CoV antiviral effects.
Crech is an old friend of aids specialists, clinically we give HIV-infected people prescription Crech, combined with other anti-HIV drugs together constitute the so-called ‘cocktail therapy’ to treat AIDS. The main component of Creech is lopinavir, which belongs to protease inhibitors, which inhibit protease function mainly by binding to viral proteases, so that the Gag-Pol polyprotein produced by the virus replication process cannot be successfully cracked, and the resulting viral particles are immature and non-infectious. The poor bioavailability of lopinavir alone, if used in combination with another protease inhibitor, Litonavir, can increase the concentration of lopinavir’s blood medicine, thereby improving the effectiveness of antiviral therapy, because litonavir can inhibit the liver’s decomposition and metabolism of lopinavir. Lopinavir and Litonavir composition of the combination of Creech, in 2000 by the United States FDA approved the listing of antiviral treatment for AIDS, although taking drugs will bring diarrhea, vomiting, high blood lipid side effects, but because of good antiviral effect, high resistance barrier, is still used as the main anti-HIV treatment drugs in clinical, Creech is also provided to PEOPLE living with HIV as a free antiviral drug in china.
The replication of coronaviruses also requires the action of viral proteases. Protease inhibitors for HIV, such as Lopinavir/Litonavir, can play an anti-coronavirus role if they can also bind to coronavirus proteases to inhibit their normal function. Previous in vitro studies have shown that Lopinavir/Litonavir inhibits the replication of MERS-CoV and SARS-CoV. At the time of the SARS outbreak, Chinese hong Kong scholars treated 41 SARS patients using Creech-in-combination ribavirin and found that patients treated with a combination of patients with ribavirin had a lower risk of developing adverse events such as acute respiratory distress syndrome (ARDS) or death 21 days after the onset of symptoms (2.4% vs 28.8%). A clinical study called MIRACLE is under way to assess whether Creech’s combination of IFN-beta is actually effective and can improve clinical outcomes in PATIENTs with MERS-CoV.
Remdesivir (RDV, GS-5734) is a new nucleoside analogue antiviral developed by Gilead. Nucleoside analogues can be used to resist viral therapy by inhibiting the synthesis of viral nucleic acids. RDV is currently being studied primarily as an experimental drug for the Ebola virus, which has strong anti-filament virus effect in vitro, and has now completed Phase III clinical trials. In 2016, The Lancet reported an Ebola case in which the 39-year-old nurse from Scotland was unfortunately infected while working in humanitarian care, was hospitalized with meningitis and found Ebola in her cerebrospinal fluid, 14 days after she received experimental treatment for RDV. The level of the virus in the cerebrospinal fluid slowly drops to an undetectable level and eventually recovers. Subsequent studies have found that RDV is not only effective for silk viruses such as the Ebola virus, but also inhibits respiratory syncytial viruses, coronaviruses, Nipah viruses, and Hendra viruses.
Through coronavirus culture of human lung epithelial cells, it was found that RDV has strong antiviral effects for MERS-CoV and SARS-CoV, Half of its effective concentrations (EC50) are 0.07 m, compared with the EC50 values of Creech for MERS-CoV and SARS-CoV, respectively, at 8?M and 17?M. Animal experiments have shown that preventive and early use of RDV can significantly reduce the level of lung tissue viral load in MICE infected with SARS-CoV and MERS-CoV, while improving lung function and alleviating symptoms. Further studies have found that RDV performs better in in vitro cell culture and in animal experiments than Creech’s combination with IFN-beta, and is the only treatment that can improve pathological damage to pulmonary tissue.
From current research data, RDV is probably the most promising anti-viral drug. However, no studies have been made on the safety and efficacy of RDV in humans.
Studies have shown that SARS-CoV’s nuclear shell protein binds closely to Cyclophilin A in human cells, helping with infection and replication. In 2011, Swiss and American scientists reported that cyclosporine (CsA) inhibited coronaviruses, and that same year, German and British scientists proved that the host’s Cyclophilins was a possible target for coronaviruses. The study drug STG-175 is a new type of cyclosporine derivative, with no immunosuppressive effect, and is a highly active Cyclophilin inhibitor in a known class compound, which may be developed into a broad-spectrum anti-coronavirus drug.
Other potentially effective drugs
Other nucleoside analogues, such as ribavirin and fabiraze, have broad-spectrum antiviral effects in vitro and theoretically have certain anti-coronavirus activity. However, because of the external celiac nucleic acidase of coronaviruses has RNA proofing, drugs such as ribavirin are greatly weakened in preventing viral nucleic acid replication. Nucleoside retrovirus inhibitors for AIDS treatment, such as tinofovvir and lamiftine, all have the effect of inhibiting RNA synthesis and whether they can play an anti-coronavirus treatment effect, it is worth observing. Widely used in the fight against influenza, such as even flower plague capsules, dredging detoxification capsules, etc. , have a broad-spectrum antiviral effect, and good safety, can be further related research to further verify its practical value in the fight against the new coronavirus.
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