Current Advances in the Treatment of BRAF-Mutant Melanoma. This medicine is available only with your doctor's . A global view of hepatocellular carcinoma: trends, risk, prevention and management. Although CSCs are similar to stem cells in terms of function, because of the lack of a negative feedback regulation mechanism for stem cell self-renewal, their powerful proliferation and multidirectional differentiation abilities are unrestricted, which allows CSCs to maintain certain activities during chemotherapy and radiotherapy [[90], [91], [92]]. The study found that there was no difference in hospitalization rates between patients who received placebo and those who received ivermectin. In addition, morphological changed caused by apoptosis, including chromatin condensation, nuclear fragmentation, DNA fragmentation and apoptotic body formation were observed. Dou Q., Chen H.N., Wang K., Yuan K., Lei Y., Li K., Lan J., Chen Y., Huang Z., Xie N., Zhang L., Xiang R., Nice E.C., Wei Y., Huang C. Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. In animal experiments, the immunohistochemical results for IVM-treated tumor tissues showed that the expression of the mitochondrial stress marker HEL was significantly increased, and the results were consistent with those of the cell experiments. The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. Reversal of P-glycoprotein-mediated multidrug resistance in vitro by doramectin and nemadectin. Caly L., Druce J.D., Catton M.G., Jans D.A., Wagstaff K.M. The article was . Hence several favorable signals were detected in a study with several structural biases against ivermectin. Dominguez-Gomez G., Chavez-Blanco A., Medina-Franco J.L., Saldivar-Gonzalez F., Flores-Torrontegui Y., Juarez M., Diaz-Chavez J., Gonzalez-Fierro A., Duenas-Gonzalez A. Ivermectin as an inhibitor of cancer stemlike cells. Smit M.R., Ochomo E.O., Aljayyoussi G., Kwambai T.K., Abongo B.O., Chen T., Bousema T., Slater H.C., Waterhouse D., Bayoh N.M., Gimnig J.E., Samuels A.M., Desai M.R., Phillips-Howard P.A., Kariuki S.K., Wang D., Ward S.A., Ter Kuile F.O. We believe that IVM can be further developed and introduced clinically as part of new cancer treatments in the near future. A review of 10 random clinical trials, with more than 1,000 participants, also didn . Activated caspase-1 can cause pro-IL-1 and pro-IL-18 to mature and to be secreted. In Didier's experiments testing the effect of IVM on lymphocytic leukemia, IVM could be used as an inhibitor of P-gp to affect MDR [22]. In this open-label randomized clinical trial of high-risk patients with COVID-19 in Malaysia, a 5-day course of oral ivermectin administered during the first week of . Pyroptosis is a type of inflammatory cell death induced by inflammasomes. IVM could block the cell cycle and induce cell apoptosis through a KPNB1-dependent mechanism in ovarian cancer [59]. Cancer stem cells and radiotherapy: new insights into tumor radioresistance. IVM inhibited the activation of EGFR and the downstream ERK/Akt/NF-kappa B signaling pathway to downregulate the expression of P-gp. Subsequently, NLRP3 Inflammasome initiates pro-caspase-1 to self-shear into mature caspase-1. In a study that screened Wnt pathway inhibitors, IVM inhibited the proliferation of multiple cancers, including the colorectal cancer cell lines CC14, CC36, DLD1, and Ls174 T, and promoted apoptosis by blocking the Wnt pathway [41]. Yan S., Ci X., Chen N., Chen C., Li X., Chu X., Li J., Deng X. Anti-inflammatory effects of ivermectin in mouse model of allergic asthma. 5. IVM has been proven to significantly inhibit the proliferation and migration of HeLa cells and promote apoptosis [56]. P2X4 receptor exacerbates ischemic AKI and induces renal proximal tubular NLRP3 inflammasome signaling. In a study that . IVM can inhibit the replication of flavivirus by targeting the NS3 helicase [17]; it also blocks the nuclear transport of viral proteins by acting on /-mediated nuclear transport and exerts antiviral activity against the HIV-1 and dengue viruses [18]. The following side effects and drug interactions that can occur with ivermectin are signs of ivermectin toxicity, according to the CDC: Abdominal pain, nausea, vomiting, and diarrhea; Dizziness; Low blood pressure; Tachycardia (an abnormally fast heart rate) Headache; Blurred vision and visual hallucinations; Confusion Kane N.S., Hirschberg B., Qian S., Hunt D., Thomas B., Brochu R., Ludmerer S.W., Zheng Y., Smith M., Arena J.P., Cohen C.J., Schmatz D., Warmke J., Cully D.F. Mechanisms of IVM-induced P2 4/P2 7/NLRP3-mediated pyroptosis. IVM is a PAK1 inhibitor in a variety of tumors, and it has good safety compared to that of other PAK1 inhibitors such as IPA-3. Autophagy-Independent Functions of the Autophagy Machinery. Therefore, IVM should be used in combination with other drugs to achieve the best effect, while the specific medication plan used to combine IVM with other drugs remains to be explored. In addition, IVM also had a cytotoxic effect on a variety of nasopharyngeal cancer cells in vitro, and the mechanism is related to the reduction of PAK1 kinase activity to inhibit the MAPK pathway. 36. The DDX23 helicase activity affects the expression of miR-12 [66]. Novel strategies to prevent the development of multidrug resistance (MDR) in cancer. It can be triggered by two activation pathways: the endogenous endoplasmic reticulum stress/mitochondrial pathway and the exogenous death receptor pathway [75,76]. Surprisingly, gemcitabine-resistant KKU214 cells showed high sensitivity to IVM, which suggested that IVM shows potential for the treatment of tumors that are resistant to conventional chemotherapy drugs. The discoverers of IVM, Japanese scientist Satoshi mura and Irish scientist William C. Campbell, won the Nobel Prize in Physiology or Medicine in 2015 [7,8]. Harbeck N., Penault-Llorca F., Cortes J., Gnant M., Houssami N., Poortmans P., Ruddy K., Tsang J., Cardoso F. Breast cancer. Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and Comorbidities: The I-TECH Randomized Clinical Trial Lim SCL, Hor CP, Tay KH, et al. Fritz L.C., Wang C.C., Gorio A. Avermectin B1a irreversibly blocks postsynaptic potentials at the lobster neuromuscular junction by reducing muscle membrane resistance. Galluzzi L., Pietrocola F., Bravo-San Pedro J.M., Amaravadi R.K., Baehrecke E.H., Cecconi F., Codogno P., Debnath J., Gewirtz D.A., Karantza V., Kimmelman A., Kumar S., Levine B., Maiuri M.C., Martin S.J., Penninger J., Piacentini M., Rubinsztein D.C., Simon H.U., Simonsen A., Thorburn A.M., Velasco G., Ryan K.M., Kroemer G. Autophagy in malignant transformation and cancer progression. However, in breast cancer cell experiments, it was also found that IVM could induce autophagy, and enhanced autophagy could increase the anticancer activity of IVM [37]. Renal cell carcinoma is a fatal malignant tumor of the urinary system derived from renal tubular epithelial cells. The PAK1-Stat3 Signaling Pathway Activates IL-6 Gene Transcription and Human Breast Cancer Stem Cell Formation. This finding led the researchers to suspect that perhaps a different type of brake, other than the PD-1/PD-L1 system, was disabling T cells in pancreatic cancer patients. Drugs targeting BRAF mutations such as vemurafenib, dabrafenib and PD-1 monoclonal antibodies, including pembrolizumab and nivolumab have greatly improved the prognosis of melanoma [71,72]. Targeting autophagy in cancer. P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders. Ivermectin neither reduced hospital admissions for worsening COVID-19 nor shortened the time that infected patients spent in the emergency room, according to data from a large randomized . Background Discovery and development of novel drugs that are capable of overcoming drug resistance in tumor cells are urgently needed clinically. The experimental results showed that IVM would preferentially targeted and inhibited CSCs-rich cell populations compared with other cell populations in MDA-MB-231 cells. The 5-year survival rate after diagnosis is approximately 47% [27,57]. Recently scientists have discovered that IVM has a strong anticancer effect. Later in December, FLCCC founder Paul Marik, the first author on the now-rejected Frontiers manuscript and a professor at Eastern Virginia Medical School, wrote a paper reviewing ivermectin that included references to debunked papers, including an observational study of ivermectin in COVID-19 patients led by now-discredited Surgisphere Corporation. On the other hand, some autophagy activators can increase the sensitivity of tumors to radiotherapy and chemotherapy by inducing autophagy, and excessive activation of autophagy can also lead to tumor cell death [[78], [79], [80], [81]]. Diana A., Carlino F., Franzese E., Oikonomidou O., Criscitiello C., De Vita F., Ciardiello F., Orditura M. Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes. Ivermectin has powerful antitumor effects, including the inhibition of proliferation, metastasis, and angiogenic activity, in a variety of cancer cells. It has a good effect on the treatment of parasitic diseases such as river blindness, elephantiasis, and scabies. A study published in the peer-reviewed American Journal of Therapeutics showed that the cost of ivermectin for other treatments in Bangladesh is around $0.60 to $1.80 for a five-day course. Drug repositioning is a shortcut to accelerate the development of anticancer drugs. Existing research is sufficient to demonstrate the great potential of IVM and its prospects as a novel promising anticancer drug after additional research. But the study provides solid evidence that ivermectin is no better than a placebo when given at a dose of roughly 30 milligrams per day over a three-day interval. The FDA first issued a warning in April 2020 that ivermectin intended for use in animals should not be used to treat COVID-19 . Nagata S. Apoptosis and Clearance of Apoptotic Cells. Gastric cancer is one of the most common malignant tumors worldwide. . 108K. Giving ivermectin with balstilimab may increase the effect of balstilimab in shrinking tumors in patients with triple negative breast cancer. IVM not only has strong effects on parasites but also has potential antiviral effects. In addition, PAK1 facilitates Wnt/-catenin signaling, make -catenin accumulate in the cytoplasm and translocate to the nucleus. Two studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE's, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo.Both selenium trials reported no inflammatory episodes during the . A new study evaluated the effect of ivermectin on time to recovery from coronavirus disease 2019 (COVID-19) in patients with mild to moderate disease. Pouliot J.F., LHeureux F., Liu Z., Prichard R.K., Georges E. Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. 3). Galluzzi L., Bravo-San Pedro J.M., Demaria S., Formenti S.C., Kroemer G. Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy. IVM could inhibit the DDX23/miR-12 signaling pathway by affecting the activity of DDX23 helicase, thereby inhibiting malignant biological behaviors. Ivermectin has been used off-label widely since the original in vitro study by Caly et al. Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin. Ivermectin is used to treat river blindness (onchocerciasis), intestinal infection from threadworms (strongyloidiasis), and other kinds of worm infections. In addition to IVM, the current avermectin family members include selamectin, doramectin and moxidectin [[2], [3], [4], [5]] (Fig. The aim of the present study was to demonstrate that ivermectin preferentially inhibited cancer stemlike cells (CSC) in breast cancer cells and downregulated the expression of 'stemness' genes. 88]. However, after using the autophagy inhibitors chloroquine and wortmannin or knocking down Bclin1 and Atg5 by siRNA to inhibit autophagy, the anticancer activity of IVM significantly decreased. Recognition of the role of Natural Products as drugs to treat neglected tropical diseases by the 2015 Nobel prize in physiology or medicine. Summary of IVM promotes programmed cell death. Juarez M., Schcolnik-Cabrera A., Duenas-Gonzalez A. Fang Y., Tian S., Pan Y., Li W., Wang Q., Tang Y., Yu T., Wu X., Shi Y., Ma P., Shu Y. Pyroptosis: A new frontier in cancer. This is a randomized, doubled-blind and placebo-controlled phase II study that will evaluate the efficacy of the early use of ivermectin plus losartan in cancer patients who present with recent diagnosis of COVID-19. In melanoma and nasopharyngeal carcinoma, IVM inhibited cell proliferation activity by inhibiting PAK1 to downregulate the expression of MEK 1/2 and ERK1/2 [69,73]. Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death. The majority of cervical cancers are caused by human papillomavirus (HPV) infection [54,55]. Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment? Gasdermin D(GSDMD)is a substrate for activated caspase-1 and is considered to be a key protein in the execution of pyroptosis [86,87]. Here, we systematically summarized the anticancer effect and mechanism of IVM, which is of great significance for the repositioning of IVM for cancer treatment. Recently, ivermectin, a well-known anti-parasite drug, was reported to share the same mechanisms with them and have anti-tumor activity. 64,74]. Draganov D., Gopalakrishna-Pillai S., Chen Y.R., Zuckerman N., Moeller S., Wang C., Ann D., Lee P.P. Abstract. JAMA Internal Medicine February 18, 2022. Loibl S., Gianni L. HER2-positive breast cancer. aAnhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, Anhui Province 233030, China, bClinical Medical Department, Bengbu Medical College, Bengbu, Anhui Province 233030, China, cDepartment of Histology and Embryology, Bengbu Medical College, Bengbu, Anhui Province 233030, China, dDepartment of Microbiology and Parasitology, Bengbu Medical College, Bengbu, Anhui Province 233030, China, eSchool of Fundamental Sciences, Bengbu Medical College, Bengbu, Anhui Province 233030, China. Arcangeli S., Pinzi V., Arcangeli G. Epidemiology of prostate cancer and treatment remarks. The inflammasome is a multimolecular complex containing pattern recognition receptor (PRR), apoptosis-associated speck-like protein containing a CARD (ASC), and pro-caspase-1. Here, we reviewed the related mechanisms by which ivermectin inhibited the development of different cancers and promoted programmed cell death and discussed the prospects for the clinical application of ivermectin as an anticancer drug for neoplasm therapy. Cancer stem cells and self-renewal. Computational searching of DrugBank, a database of approved drugs, was performed using the principles of twodimensional similarity . Liu Y., Fang S., Sun Q., Liu B. Anthelmintic drug ivermectin inhibits angiogenesis, growth and survival of glioblastoma through inducing mitochondrial dysfunction and oxidative stress. Wurth R., Thellung S., Bajetto A., Mazzanti M., Florio T., Barbieri F. Drug-repositioning opportunities for cancer therapy: novel molecular targets for known compounds. Ovarian cancer is a malignant cancer that lacks early clinical symptoms and has a poor therapeutic response. Ivermectin(IVM) is a macrolide antiparasitic drug with a 16-membered ring derived from avermectin that is composed of 80% 22,23-dihydroavermectin-B1a and 20% 22,23-dihydroavermectin-B1b [1]. Therefore, CSCs have been widely recognized as the main cause of recurrence after treatment [93,94]. IVM regulates the tumor microenvironment and mediates immunogenic cell death, which may be a new direction for research exploring anticancer mechanisms in the future. Gong T., Liu L., Jiang W., Zhou R. DAMP-sensing receptors in sterile inflammation and inflammatory diseases. A large, randomized study of COVID-19 patients in Brazil shows that being treated with ivermectin has little or no benefit. PRR can identify pathogen-associated molecular patterns (PAMPs) that are structurally stable and evolutionarily conserved on the surface of pathogenic microorganisms and damage-associated molecular patterns (DAMPs) produced by damaged cells [84,85]. Overall, the specific environment of tumor cells will determine whether autophagy enhances or inhibits tumor development and improving autophagy activity has also become a new approach in cancer therapy. 5). Experiments confirmed that IVM could significantly inhibit the proliferation of five renal cell carcinoma cell lines without affecting the proliferation of normal kidney cells, and its mechanism may be related to the induction of mitochondrial dysfunction [48]. Interestingly, IVM also restored the sensitivity of the triple-negative breast cancer to the anti-estrogen drug tamoxifen [36], which also implies the potential for IVM to be used in endocrine therapy. It is impossible to prove a negative, so the TOGETHER trial cannot prove that ivermectin is not useful in treating COVID. PAKs in Human Cancer Progression: From Inception to Cancer Therapeutic to Future Oncobiology. A word about safety There were no serious ivermectin-related adverse events. Nasopharyngeal carcinoma is a malignant tumor derived from epithelial cells of the nasopharyngeal mucosa. Introduction. In recent years, many new chemotherapeutic drugs have entered the clinic, but tumor cells are prone to drug resistance and obvious adverse reactions to these drugs. Ivermectin has been touted as a treatment or prevention method for COVID-19 . Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. Intuyod K., Hahnvajanawong C., Pinlaor P., Pinlaor S. Anti-parasitic Drug Ivermectin Exhibits Potent Anticancer Activity Against Gemcitabine-resistant Cholangiocarcinoma In Vitro. Zanconato F., Cordenonsi M., Piccolo S. YAP and TAZ: a signalling hub of the tumour microenvironment. Expansion and evolution of cell death programmes. As shown in In this study, we sought to explore whether ivermectin (IVM), a macrolide antiparasitic agent, could overcome the resistance of cancer cells to the therapeutic drugs. Udensi U.K., Fagbenro-Beyioku A.F. Liu J., Liang H., Chen C., Wang X., Qu F., Wang H., Yang K., Wang Q., Zhao N., Meng J., Gao A. Ivermectin induces autophagy-mediated cell death through the AKT/mTOR signaling pathway in glioma cells. Recently, ivermectin has been reported to inhibit the proliferation of several tumor cells by regulating multiple signaling pathways. Elsevier Public Health Emergency Collection, HelaColorectal cancer (CC14, CC36, DLD1,Ls174 T)Ovarian cancer (SKOV3, OVCAR3, CAOV3)Renal cell carcinoma (SW-839, Caki-2, 786-O, A498, ACHN)Leukemia(K562, primary CD34, Glioma (U251, C6)Breast cancer(MCF-7, MDA-MB-231)Melanoma (SK-MEL-28), Breast cancer, Ovarian cancer, Nasopharyngeal carcinoma, Melanoma, Prostate cancer, Lung cancer Colorectal cancer. Kumar R., Gururaj A.E., Barnes C.J. Campbell W.C., Fisher M.H., Stapley E.O., Albers-Schonberg G., Jacob T.A. Programmed cell death mediated by autophagy after IVM intervention and the enhancement of the anticancer efficacy of IVM by regulating autophagy are interesting topics. RAS activation directly initiates PAK1, MAPK and PI3K/Akt pathway. Triple-negative breast cancer (TNBC) refers to cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2(HER2) and is the most aggressive subtype of breast cancer with the worst prognosis. Additionally, it has been confirmed that PAK1 is the key target of IVM that mediates its anti-melanoma activity, and IVM can also significantly reduce the lung metastasis of melanoma in animal experiments. The phenomenon of IVM-induced autophagy has also been reported in glioma and melanoma [ Medicinal chemistry strategies to discover P-glycoprotein inhibitors: An update. Only the paste. However, to date, no exact target for IVM action has been found. Nishio M., Sugimachi K., Goto H., Wang J., Morikawa T., Miyachi Y., Takano Y., Hikasa H., Itoh T., Suzuki S.O., Kurihara H., Aishima S., Leask A., Sasaki T., Nakano T., Nishina H., Nishikawa Y., Sekido Y., Nakao K., Shin-Ya K., Mimori K., Suzuki A. Dysregulated YAP1/TAZ and TGF-beta signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice. PAK1 can induce MEK1/2 and ERK1/2 activation by RAF and increase PI3K/Akt signaling by PDK1. But the question of which cancers Ivermectin has been proven effective is a constant source of questions. IVM.YAP1 plays an oncogenic role in tumorigenesis, indicating the possibility of the use of IVM as a YAP1 inhibitor for cancer treatment . Wagstaff K.M., Sivakumaran H., Heaton S.M., Harrich D., Jans D.A. The relationship between apoptosis and autophagy is very complicated, and the cross talk between the two plays a vital role in the development of cancer [82]. 672. An early study using cells in petri dishes suggested that ivermectin has antiviral properties at very high concentrations and could inhibit the pandemic coronavirus, SARS-CoV-2. Written by Carolyn Crist. This was related to the induction of mitochondrial dysfunction and oxidative stress. DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis. We formerly reported that the combination of dichloroacetate, omeprazole, and tamoxifen blocked cancer progression by reducing lactic acid production and inducing superoxide production. Our scientists pursue every aspect of cancer researchfrom exploring the biology of genes and cells, to developing immune-based treatments, uncovering the causes of metastasis, and more. We are experimenting with display styles that make it easier to read articles in PMC. Wang J., Xu Y., Wan H., Hu J. Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment. Several studies showed that the ivermectin has antitumor effects on a variety of cancer cells. 2 IVM could significantly reduce the mitochondrial membrane potential and inhibit mitochondrial respiration and ATP production. Despite the fact that these trials found ivermectin inferior to the cream it was being tested against, it still won approval due to its low cost and ease of administration. The presence of the mitochondrial fuel acetyl-L-carnitine (ALCAR), and the antioxidant N-acetyl-L-cysteine (NAC), could reverse IVM-induced inhibition. For example, it was found in SK-MEL-28 melanoma cells that IVM can promote apoptosis as well as autophagy [74]. Formulated as a lotion, ivermectin is safe enough to be administered as an over-the-counter treatment for head lice in kids. This group explores and celebrates the successes of the repurposed drug Fenbendazole to help with cancer treatment. Furthermore, Diaos study showed that IVM could inhibit the proliferation of the canine breast tumor cell lines CMT7364 and CIPp by blocking the cell cycle without increasing apoptosis, and the mechanism of IVM may be related to the inhibition of the Wnt pathway [33]. A few weeks ago, William C. Campbell and Satoshi Omura, the scientists who developed ivermectin, won a Nobel Prize for the research that led to development of the drug, which has vastly reduced . 4), but there is no specific evidence to prove this speculation. Find NCI-Supported Clinical Trials; What Are Clinical Trials? In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in . It works by interfering with the nerve and muscle functions of worms, by paralyzing and killing them. However, NAC reversed the effect of IVM, which indicated that IVM increased TFE3-dependent autophagy through the ROS signaling pathway. Wang's experiment found that IVM could selectively induce mitochondrial dysfunction and oxidative stress, causing chronic myeloid leukemia K562 cells to undergo increased caspase-dependent apoptosis compared with normal bone marrow cells [53]. Interestingly, IVM could also show activity against BRAF wild-type melanoma cells, and its combination with dapafinib could significantly increase antitumor activity. p21-activated kinases in cancer. Earlier, we mentioned the role of IVM in docetaxel-resistant prostate cancer [50] and gemcitabine-resistant cholangiocarcinoma [44]. Gao A., Wang X., Xiang W., Liang H., Gao J., Yan Y. With the development of derivatives of the avermectin family that are more efficient and less toxic, relevant research on the anticancer mechanism of the derivatives still has great value. It has been widely used in humans for many years, and its various pharmacological properties, including long- and short-term toxicological effects and drug metabolism characteristics are very clear. IVM halted the cell cycle in S phase and promoted apoptosis. This suggests that IVM may be used as a potential CSCs inhibitor for cancer therapy. Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis with survival of less than 5 years when advanced. Mingyang Tang, Xiaodong Hu, [], and Qiang Fang. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection . Antoszczak M., Markowska A., Markowska J., Huczynski A. Abstract. The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro. It included data from Surgisphere, a company that also provided inaccurate patient data . Katz N., Araujo N., Coelho P.M.Z., Morel C.M., Linde-Arias A.R., Yamada T., Horimatsu Y., Suzuki K., Sunazuka T., Omura S. Ivermectin efficacy against Biomphalaria, intermediate host snail vectors of Schistosomiasis. . On the other hand, ivermectin promotes programmed cancer cell death, including apoptosis, autophagy and pyroptosis.