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J Thai Trad Alt Med                                   Vol. 21  No. 2  May-Aug  2023  329




                 Introduction and Objectives            acts with ACE2 that directly affects the fitness
                                                                                     [3]
                 Since the Coronavirus disease 2019     and transmissibility of the virus. Therefore,
            (COVID-19) outbreak in Wuhan, China in      inhibition of ACE2 or TMPRSS2 and other
            December 2019, more than 460 million people   host-target molecules could limit the transmis-
                                                   [1]
            have been infected and 6 million have died.    sion in the early phase of infection.  ACE2 and
            The disease is caused by severe acute respira-  TMPRSS2 have been studied and identified to
            tory syndrome coronavirus 2 (SARS-CoV-2), a   be the main targets of SARS-CoV-2 inhibitors.
                                                                                              [4-7]
            coronavirus with a spike protein. The receptor-  ACE2 and TMPRSS2 are mostly expressed not
            binding domain of the spike protein on the   only in lung tissue but also in kidney, oesopha-
                                                                                             [8-9]
            viral envelope of SARS-CoV-2 can directly and   gus, colon, heart, brain and other organs.
            specifically bind to angiotensin-converting   Patients infected with the virus might have
            enzyme 2 (ACE2), a membrane-associated      symptoms such as fever, cough, shortness and

            enzyme. The SARS-CoV-2 spike protein can    difficulty in breathing and some complications
            be cleaved and activated by transmembrane   of pneumonia, kidney failure or even death. [10]
            proteases, including serine 2 (TMPRSS2) be-      In Thailand, some people have turned

            fore being endocytosed into host cells. Once   to using medicinal plants or alternative
            the virus enters the cell, the virus also needs   medicines to alleviate symptoms caused by
            the PIKfyve enzyme to form an endosome and   the infection with most showing antipyretic

            transport virus particles in the cytoplasm.    properties or the inhibition of  virus-caused
            This process also needs cathepsin L protease,   disease.  Traditional drug formulations in the
            which is responsible for endosome maturity.    National List of Essential Medicine including

            The Inhibition of PIKfyve and cathepsin L pro-  Ya Prasa Pro Yai, Ya Ha Rak and Ya Chanthalila
            tease has been shown to be effective against   formulations have been widely used for alle-

            SARS-CoV-2, Ebola virus (EBOV) and African   viating fever  during the pandemic and have
            swine fever in the early and mid-stages of the   been prepared in several forms (capsules, dried
                     [2]
            infection.   Presently, the virus continues to   powder and tablets).  Formulations of these
            mutate producing different strains including   traditional drug have been published on the
            alpha (B.1.1.7), beta (B.1.351), gamma (P.1),   website of Thai Food and Drug Administration

            delta (B.1.617.2) and omicron (B.1.1.529).    (Thai FDA).  Ya Prasa Pro Yai is specifically
                                                                  [11]
            Each mutation has an altered sequence at the   used to treat flu, stomach pain, flatulence and
            receptor-binding domain (RBD), which inter-  anorexia in children. The formulation  con-
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