Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic. 1. Introduction The outbreak of coronavirus SARS-CoV-2 in Wuhan, China in December 2019, the cause of Corona Virus Disease of 2019 (COVID-19), represents a pandemic threat to global health [1,2]. The WHO declared COVID-19 as a pandemic on March 11th 2020. The outbreak has spread to more than 185 countries with more than 3,200,000 confirmed cases, more than 230,000 confirmed deaths and more than 1,000,000 total recoveries worldwide as of May 1st 2 2020 [3]. Hundreds of millions of lives have been affected as a result of mandatory isolations/quarantines. This pandemic has the potential to overwhelm national healthcare systems, and have major consequences on global economy if SARS-CoV-2 spread and virulence is not contained, or effective treatments are not developed.Coronaviruses are grouped into alpha, beta, gamma, and delta classes. Coronaviruses can infect both humans and animals. The source of the beta coronavirus SARS-CoV-2 is believed to be bats, which carry the virus with no signs of disease [4]. Beta coronaviruses caused earlier outbreaks of severe acute respiratory syndromes (SARS), including SARS-CoV (2002/2003 in Guangdong, China) and Middle East Respiratory Syndrome virus MERS-CoV (2012 in Saudi Arabia) [5]. Beta coronaviruses are pathogenic for humans and have a single stranded RNA genome, encapsulated by a membrane envelope [6]. The coronavirus crown-like ("corona") morphology is created by transmembrane spike glycoproteins (S proteins) that form homotrimers protruding from the viral surface [7]. The S proteins of SARS-CoV and SARS-CoV-2 display structural homology and conserved ectodomains, so earlier strategies employed to prevent binding of SARS-CoV to its host cell receptor angiotensin-converting enzyme 2 (ACE2) may be relevant, since SARS-CoV-2 also employs ACE2 for cell entry [8,9]. ACE2, an exopeptidase expressed on epithelial cells of the respiratory tract, may constitute a pharmacological target to limit cell entry of SARS-CoV-2. The established antimalarial drugs chloroquine and hydroxychloroquine ha...

The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of “mast cell activation syndrome” (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a “consensus” (re-termed here as “consensus-1”). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as “consensus-2”), resembling “consensus-1” in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by “consensus-2” criteria has potential to be problematic, but underdiagnosis by “consensus-1” criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.

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: Cancer stem cells (CSCs) constitute a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity, and the ability to give rise to the heterogeneous lineages of cancer cells that comprise the tumor. CSCs exhibit intrinsic mechanisms of resistance to virtually all conventional cancer therapeutics, allowing them to survive current cancer therapies and to initiate tumor recurrence and metastasis. Different pathways and mechanisms that confer resistance and survival of CSCs, including activation of the Wnt/β-catenin, Sonic Hedgehog, Notch, PI3K/Akt/mTOR and STAT3 signaling pathways, expression of aldehyde dehydrogenase 1 (ALDH1) and oncogenic microRNAs, and acquisition of epithelial-mesenchymal transition (EMT), have been identified recently. Certain phytochemicals, in particular curcumin, epigallocatechin-3-gallate (EGCG), sulforaphane, resveratrol and genistein have been shown to interfere with these intrinsic CSC pathways in vitro and in human xenograft mice, leading to elimination of CSCs. Moreover, recent clinical trials have demonstrated therapeutic efficacy of the five phytochemicals, alone or in combination with modern cancer therapeutics, and in various types of cancer. Since current cancer therapies fail to eradicate CSCs, leading to cancer recurrence and progression, targeting of CSCs with phytotochemicals such as curcumin, EGCG, sulforaphane, resveratrol and genistein, combined with each other and/or in combination with conventional cytotoxic drugs and novel cancer therapeutics, may offer a novel therapeutic strategy against cancer.

Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARSCoV- 2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit spread of SARS-CoV-2 and morbidity and mortality of the COVID-19 pandemic.