Implementation of Modified Shutdown Protocol during COVID 19 Pandemic for Risk Mitigation at Manufacturing Sites

A well-planned pandemic protocol and define emerging risk preparedness checklist during pandemic help to ensure the shutdown is conducted safely and well efficiently so that manufacturing sites can be returned to normal operation as per defined timeline. As such we have implemented shutdown protocol to mitigate Occupational Health Hazards risk. The major challenge to manage the large workforce and additionally prevention of COVID 19 spread among workforces. COVID 19 risk management is a proactive preparedness which was included in revised shutdown protocol and implanted across all sites. This strategy would be great help to mitigate the risk and successfully completion of shutdown at respective manufacturing location. Methods & Guidelines: Methods: To managed shutdown risk management during a pandemic, the following methodology was considered during planning. * The first step was virtual meeting with the plant team to understand the shutdown job, list of hazardous activities, the number of the workforce, days of shutdown, etc. * The second step was to plan a Sustainable COVID 19 management program including testing and create a Bio bubble for all the employees and business partners involved in the shutdown. * The third step was to determine potential exposure to chemical, physical and biological agents, including medical OH requirements, the review of existing control measures. * The fourth step was to verification, planning, and execution of all requirements in the prescribed checklist and plant round to identify any gaps followed by a plant shutdown meeting. Result(s): Pandemic Management protocol and defined OH-IH emerging risk preparedness checklist during the pandemic had helped to ensured that Shutdown activities were well managed with proactive control program and robust system. Emerging risk details of one of the manufacturing sites are mentioned below. * Total no of workforce health screening: 25000 Nos Approx. * 24x7 ACLS ambulance with medical officer and nursing staff a defined job location * RT PCR testing before entry and periodic testing * Availability of antidotes & Safety Data Sheet * Basic first-aider training and shift wise availability * Arrangement of accommodation (Bio Bubble) till completion of shutdown Conclusion(s): Modified shutdown protocol with inclusion of COVID 19 management is great tool/approach to mitigate OH hazard including COVID 19 in shutdown and comprehensive monitoring of hazardous activities. The recommended control measures would help to ensure the next turnaround project will be completed with a well-defined checklist having all controls in place.

Intentional Taxus Baccata Ingestion Presenting with Cardiogenic Shock and Ventricular Tachycardia

Background The prevalence of anxiety and depression has increased following the COVID pandemic. Young women are disproportionally at risk of suicidal behaviors. Ingestion of Taxus baccata (English Yew) may lead to cardiotoxicity and death. Intoxication is known to be resistant to standard treatments with no effective antidotes. Case A 20-year-old female with a history of major depressive disorder presented to our emergency department unresponsive in pulseless ventricular tachycardia (VT) (figure 1A). She underwent CPR and achieved ROSC, however, was persistently hypotensive despite multiple pressors and was subsequently placed on VA ECMO. Review of a home journal revealed a plan to ingest 50 grams of Yew with suicidal intent. Decision-making Taxoids have been reported to have similar properties to digoxin and therefore digoxin-specific FAB antibodies were administered. She was also started on amiodarone and lidocaine for management of VT. After 3 hours she converted into sinus rhythm and had no further episodes of VT. Her clinical course was complicated by severe LV dysfunction and dilation while on VA-ECMO necessitating placement of an LV impella. By day three, all mechanical support was weaned off and she had normalization of her EF. Patient was discharged to an inpatient psychiatry facility on day 7 of hospitalization. Conclusion Ingestion of English Yew with suicidal intent is rare but may cause cardiogenic shock and VT requiring aggressive hemodynamic support until the toxin is metabolized. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

US shortages of agents used to treat poisonings over the last 10 years (2012-2021)

Background: Drug shortages represent a longstanding challenge for healthcare providers, including toxicologists, who continue to confront scarcities of antidotes and other agents used to treat poisonings. Prior research examining availability of drugs with toxicologic applications from 2001 to 2013 demonstrated broad shortages including anticholinergic, cholinergic, and cyanide antidotes, anti-hypoglycemics, chelators, antivenom, naloxone, sedative- hypnotics, and decontamination products, many of which were unresolved and involved xenobiotics without therapeutic alternative. Reports of vital agents being scarce or unobtainable have continued since 2013, and new pressures on global and US (United States) supply chains have emerged, most notably the COVID-19 pandemic. Given this, up-to-date analysis of shortages of agents used to treat poisonings is needed. Method(s): US drug shortage data from January 2012 to December 2021 were obtained from the University of Utah Drug Information Service. Shortage data for agents used to treat poisonings were analyzed. Information on drug type, formulation, shortage reason, shortage duration, number of manufacturing sources, substitute availability, and substitute agent shortage during the study period were investigated. Result(s): 1570 drug shortages were reported during the study period;230 (14.6%) involved agents used to treat poisonings. Of the 230 shortages, 21.3% were unresolved as of December 2021. Mean shortage duration was 13.6 months. The longest shortage involved intravenous calcium gluconate and lasted 78 months. Intravenous dextrose products were the agent most frequently affected by shortage, with 20 shortages in total. 58 agents had multiple shortages. Total shortages peaked in 2017 with 33 shortages reported. 20 shortages were reported in 2020 and 24 in 2021 during the COVID-19 pandemic. 10.9% of shortages involved single-source products;however, this number is limited by incomplete reporting. 80.9% of shortages involved parenteral products. Agent classes with the most shortages reported were: Sedative-hypnotics (12.2% of shortages), anti-hypoglycemics (9.6%), anticoagulant reversal (7.8%), vitamins/electrolytes (7.4%), blood pressure support (7%), antihypertensives (6.5%), antimuscarinic delirium (4.8%), and chelators (4.3%). Three naloxone shortages were reported, one of which is ongoing due to increased demand. Buprenorphine and methadone shortages were reported but are resolved as of December 2021. New shortages of multiple pressors and flumazenil were reported. The most common reason for shortage was a manufacturing issue, occurring in 36.1% of shortages. Shortage reason was not reported 37.8% of the time. For 77% of shortages an alternative therapeutic agent was available, however 97% of alternatives were also affected by shortage at some point during the study period. Conclusion(s): Shortages of agents used to treat poisonings remain problematic. For the time period 2011-2021 previously reported shortages of many products persist and new shortages have emerged. The ongoing naloxone shortage is particularly concerning given the continued rise in drug overdose deaths in the US in 2021, as are shortages of buprenorphine and methadone used to treat opioid use disorder. Despite supply chain stressors, total shortages did not peak during the COVID-19 pandemic.

THE BIG IMPACT OF SMALL CHANGES IN NARROW THERAPEUTIC INDEX DRUGS

CASE: An 84-year-old woman with atrial fibrillation on Digoxin presented with acute onset of confusion associated with a week history of abdominal pain, vomiting, and poor fluid intake. A few days prior, Amiodarone was added to her drug regimen which included Lasix. Additionally, she received the COVID-19 booster vaccine which led to a viral-like syndrome resulting in dehydration. The patient was afebrile, normotensive, but bradycardic. EKG showed a prolonged PR interval and scooped ST segments. Labs showed hyperkalemia, pre-renal acute kidney injury (AKI), and a Digoxin level of 4.3 ng/mL (therapeutic range: 0.8-2.0 ng/mL). Digoxin and Lasix were held and Digoxin antidote, Digibind, was administered with normalizing heart rate, potassium, and clinical improvement. IMPACT/DISCUSSION: Digoxin is used to slow conduction in atrial fibrillation and increase cardiac contractility in heart failure. It inhibits the membrane sodium-potassium-adenosine triphosphatase pump (Na/K ATPase), resulting in increased cytosolic calcium and subsequent cardiac contractility and automaticity. In turn, this can also cause premature ventricular contractions and tachycardia. In the carotid sinus, increased baroreceptor firing and subsequent increased vagal tone occurs which can cause bradycardia, atrioventricular blocks, hypotension, and GI symptoms. In skeletal muscle, hyperkalemia can result due to the abundance of Na/K ATPase pumps. Digoxin has a narrow therapeutic index with serum levels easily affected by many commonly prescribed drugs by way of decreasing renal clearance, inhibiting P-glycoprotein, and inducing secondary electrolyte disturbances. That said, drug dosing should be individualized with close monitoring to avoid potentially life-threatening effects that may result with even mildly increased digoxin levels. Acute toxicity manifests as non-specific GI, and neurologic symptoms (confusion, lethargy, visual changes), hyperkalemia, and brady or tachy-arrhythmias. Treatment is with digoxin specific fragment antigen binding (Fab) antibody, Digibind, which binds digoxin, inactivating it within 6-8 hours. Postadministration, digoxin serum testing cannot distinguish free verse bound drug;therefore, drug levels remain elevated for days to weeks until the FabDigoxin complex is excreted. In the case above, the viral-like-syndrome after the booster vaccine with subsequent AKI secondary to dehydration likely precipitated Digoxin toxicity. Accompanying drug interactions of diuretics causing dehydration and hypokalemia, P-glycoprotein inhibitors (Amiodarone, Verapamil, Diltiazem, Quinidine), and ACE inhibitors can further worsen renal clearance and culminate in Digoxin toxicity. CONCLUSION: Given Digoxin's narrow therapeutic index, small clinical changes such as post COVID-19 vaccine flu-like symptoms, dehydration, and medication changes can manifest drug toxicity. Therefore, attentive monitoring of accompanying comorbidities and drug interactions is imperative at preventing catastrophic toxic effects.

Anticoagulants: dose control methods and inhibitors

These days, anticoagulants are in great demand. They are used as a prophylaxis for thromboembolic complications in various diseases and conditions in general therapeutic practice, cardiology, neurology, as well as obstetrics to manage high-risk pregnancies. The relevance of anticoagulants competent use has come to the fore in connection with the emergence of a new disease – COVID-19 and its serious complications such as developing thrombotic storm, in which the timely applied anticoagulant therapy is the key to the success of therapy. The risk of bleeding should be considered when using any anticoagulant. Age, impaired renal function and concomitant use of antiplatelet agents are common risk factors for bleeding. Moreover, only vitamin K antagonists and heparin have specific antidotes – vitamin K and protamine, respectively. Inhibitors of other anticoagulants are universal presented as inactivated or activated prothrombin complex concentrate and recombinant factor VIIa. Hemodialysis effectively reduces dabigatran concentration, activated charcoal is effective in the case of recent oral administration of lipophilic drugs. Research on new antidotes of currently available anticoagulants is under way, similar to testing of new types of anticoagulants that are sufficiently effective in preventing and treating thromboembolic complications with minimal risk of hemorrhagic. The main contraindication to anticoagulants use is the doctor's ignorance of the mechanisms of drug action and opportunities for suppressing its effect.

Role of the Unani System of Medicine in Countering Epidemic Diseases, Considering Coronavirus Pandemic -19

Since December 2019 world faces a respiratory pandemic named Coronavirus disease-19 (COVID-19). COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The term epidemic was coined by Hippocrates who is considered the father of Unani medicine which is based on four humours. In the Unani System of Medicine (USM) equivalent term for the epidemic is Wabā'. In classical Unani literature symptoms of Nazla-i-Wabā'iyya and Humma-i-Wabā'iyya closely resemble the symptoms of COVID-19. Major manifestations of this outbreak are cough, fever, headache, nausea, and breathlessness. This pandemic takes place due to a change in the quality of the surrounding air. We searched different databases electronically using the terms “COVID-19 or Coronavirus”, “Wabā or infectious disease”, “Unani immunomodulators”, ''Herbal immunomodulators'', ''Anti-viral herbal drugs'', Herbal fumigation and “Nazla-i-Wabā'iyya or Nazla Wabā'ī”. We also gone through different classical textbooks of USM available in the NRIUMSD library. We reviewed the concept of Wabā', its prevention, and management strategies available in USM. We also searched antiviral, immunomodulation, fumigation activities of Unani drugs. Unani physicians advocated general measures of physical distancing, health hygiene, isolation, quarantine, and immunomodulation. As a preventive measure, various immunomodulatory drugs like Asgandh, Aam, Babuna, Gilo, Satawar, and Kalonji and antidotes such as Tiryāq Wabā'i have been described in the literature. The ingredients of Tiryāq-i-Wabā'i include Aloe barbedensis, Crocus sativus, and Commiphora myrrha. Several fumigants like Sandal, Ood, Kafoor, Loban, and Jhau are also mentioned in the management of the epidemic. For symptomatic management various antiviral, antipyretic and antitussive drugs are described well. Many evidence-based studies have already been reported for single drugs and formulations used in the USM.The Khamira Marwareed possesses antiviral, cardiotonic, and immunomodulatory activity. Single drugs such as Khaksi, Asgandh, Adusa, Chiriata, and Zanjabeel possess antipyretic, immunomodulatory, antitussive, antibacterial, and antiviral activities respectively. The knowledge from classical Unani literature and scientific researches may be useful in the prevention and management of COVID-19 like epidemic diseases. This review article aims to find out the concept of the pandemic, prevention, and management strategies existing in the USM.

Methanol intoxication outbreak during the COVID-19 pandemic in Cape Town, South Africa: a case series

Objective: Methanol poisoning may result in significant morbidity and mortality, particularly during poisoning outbreaks in lowand- middle-income countries (LMIC) [1]. Although not readily available to the public in South Africa, methanol may be used as a substitute for ethanol in alcoholic beverages or to fortify illicit spirits. Following the announcement of the global COVID-19 pandemic, the South African government declared a State of Emergency in March 2020 which amongst other things prohibited the consumption, sale and transportation of alcohol [2]. We aim to describe the clinical presentation, diagnosis, treatment and outcome of a series of cases presenting to a Cape Town hospital after reportedly drinking illicit alcohol. Case series: We performed a retrospective case record review using the available records for 19 of 24 patients presenting to False Bay Hospital during June 2020 with presumed methanol poisoning. Almost all the patients were male (n=18), with a mean age of 35.1 years (SD =7.3). At least half of the patients had central nervous system effects (n=12;headache, ataxia, confusion, weakness), as well as gastrointestinal symptoms (n=10;abdominal pain, nausea, vomiting), and 5 patients reported visual loss. Time from exposure to presentation varied from 12 hours to 8 days, with 47.4% (n=9) presenting within the first 24 hours. On admission, venous blood gas samples from the patients showed the following mean values: pH of 7.14 (SD =0.23);serum bicarbonate 17.4 (SD =8.5) mmol/L;base deficit of -7.8 (SD =11.6) mmol/L, and lactate concentration of 4.1 (SD =4.0) mmol/ L. Assays to measure methanol or formate concentrations were not performed as these are not routinely available. Ten patients (52.6%) received both ethanol via nasogastric tube and intravenous sodium bicarbonate. Haemodialysis was considered for one patient but never started due to intensive care unit (ICU) resource constraints with COVID-I9 admissions. The mortality rate was 26.3% (n=5) and one patient had ongoing visual loss. Conclusion: To the authors' knowledge, this is the first published data concerning a methanol poisoning outbreak in South Africa. As described in other LMICs, the mortality rate was high, diagnosis was difficult, and access to ethanol antidote and supportive care was challenging, particularly during the COVID-19 pandemic. (Table Presented).

Anticholinergic poisoning associated with frozen spinach

Objective: In some countries the Thursday before Easter is called Green Thursday according to the Christian calendar, and in this tradition, a green meal should be eaten on this day to ensure good health throughout the coming year. A few days before Easter the National Toxicological Information Centre (NTIC) registered an increased number of toxicological consultations following consumption of deep-frozen spinach puree which was sold in retail chains throughout Slovakia. Symptoms were characteristic of tropane alkaloid intoxication and experts suspected the spinach was contaminated with Jimson weed (Datura stramonium). Methods: A retrospective analysis of all telephone calls concerning frozen spinach products from the database of the NTIC from 1 March 2021 to 30 April 2021 was conducted. Results: The NTIC received 93 telephone calls from people who had consumed frozen spinach, of which 64 people (7 children) had mild symptoms of intoxication (PSS1) and 5 moderate poisoning (PSS2). The most commonly reported symptoms were malaise, dizziness, dry mouth, mydriasis and blurred vision that appeared within 1 to 2 hours after ingestion. Patients with moderate symptoms of intoxication were confused, disoriented and had hallucinations. The symptoms disappeared spontaneously within 48 hours. The country was in a state of emergency that had been declared before Easter due to COVID-19 and people were afraid to attend hospitals. Therefore, only 7 out of 69 people with symptoms arrived in hospital. Only 3 patients were hospitalised. Treatment was symptomatic, without the administration of an antidote physostigmine. The other patients were treated at home. Unfortunately, an increased number of consultations was recorded on Good Friday afternoon, when it was very difficult to initiate a wide scale alert informing the public through the media. Over the Easter weekend, the NTIC alerted the public to avoid the contaminated spinach via social media and the NTIC website. The State Veterinary and Food Administration of the Slovak Republic arranged analyses of contaminated frozen spinach samples in an accredited laboratory and this confirmed the presence of atropine and scopolamine. Conclusion: Datura stramonium grew with spinach in the field as a weed and contaminated the spinach due to insufficient entry and exit controls. As a result of promptly spreading information and informing the public about the contaminated spinach product in the media, further cases of poisoning over the Easter holidays were successfully averted.

A curious method to commit suicide

Objective: The COVID-19 pandemic has generated an increase in anxiety-depressive disorders throughout society, with an evident impact on children and adolescents, further precipitated by limitations in social activities during confinement. The increase in home isolation with abuse of new technologies, often far from parental control, involves risky situations such as the case we present. Case report: A 19-year-old man diagnosed with major depressive disorder, with psychiatric admissions since July 2019 for overdose with suicidal intent was home treated with methylphenidate 40mg, mirtazapine 15mg and vortioxetine 10mg. In August, the patient was searching for information on the Internet about euthanasia and suicide without pain in different pages and Internet forums. He bought two products online (by Amazon) that seemed effective for this purpose: a kilogram packet of sodium nitrate and a bottle of antifreeze. Finally, he decided on the first option due to the risk of suffering after ingesting antifreeze. On August 26 (4:00 pm), he ate a tablespoon (80 mg) of sodium nitrate. He developed dyspnea and feeling overwhelmed so he decided to informed his family of what he had done and an ambulance was called. He was transferred to hospital and given oxygen. At 7:00 pm in the emergency department he was noted to have a greyish coloration (“hot dead” appearance) with poor respiratory mechanics, tachycardic, tachypneic, with signs of peri-arrest: blood pressure 96/50mmHg, heart rate 145 bpm, respiratory rate 30/min, oxygen saturations 70%. He also had uncoordinated movements, and could not obey orders. The patient was sedated for intubation and mechanical ventilation. An arterial blood gas analysis performed after intubation showed: pH 7.35, pO2 165mmHg, pCO2 24mmHg, base excess -10.4, bicarbonate 14.5 mEq/L, potassium 3.1 mmol/L, methemoglobin 83%, carboxyhemoglobin 1.4%, lactate 13.3mmol/L. Methylene blue 1% (75mg intravenously) and activated charcoal by nasogastric tube were administered (after intubation). Later, he was admitted to the intensive care unit (9:20 pm). Physicians from this unit decided to administrate hydroxocobalamin (5 g intravenously at 00.39 am). The patient was extubated and discharged from the intensive care unit 36 hours after his admission to the department of Internal Medicine, without clinical complications;later he was transferred to Psychiatry Department. Conclusion: The toxic mechanism of sodium nitrate is related to the generation of methemoglobin. This patient survived a potentially lethal methemoglobin level following intentional ingestion of sodium nitrate with prompt administration of an antidote.

COVID-19 and methanol poisoning in Azerbaijan

Objective: The global pandemic of coronavirus SARS-CoV-2 has been a serious stress test for healthcare systems in many countries, with a significant impact on the structure and number of acute chemical poisonings. The aim of this study was to examine the impact of the COVID-19 pandemic on the toxic-epidemiological situation in Azerbaijan. Methods: We conducted a comparative analysis of the database of the Poison Center in Baku during the 9 months of the pandemic period (20 March - 21 December 2020) with the data of the same period in 2019 and the previous decade (2009-2018). Results: The alarming dynamics of a significant increase in the number of alcohol surrogates, primarily methanol poisoning, was revealed. In the 10-year period 2009-2018, alcohol surrogates intoxication was only 0.09% (18 patients) of total poisoning cases (20,266), but during the study period of 2020 increased to 3.4% (32 patients of 946 poisoning cases). The mortality rate in the ethanol and alcohol surrogate intoxication group in 2019 was 7.5% (8/ 106) versus 28.3% (30/106) in March-December 2020. All fatal cases in the alcohol surrogate poisoning cohort were related to methanol, thus, the mortality rate of this pathology was 61.5% (16/26). At the same time, no case of methanol poisoning was recorded in March-December 2019, and in the previous decade (2010-2018), only 1 case of methanol intoxication was recorded. The source of methanol during the pandemic was ingestion of counterfeit medical alcohol and alcohol-containing disinfectant products purchased by the victims themselves in the pharmacy network. Conclusion: The COVID-19 pandemic and quarantine measures had a significant impact on the epidemiology of poisoning in Azerbaijan, with an increase in cases and mortality of methanol poisoning. The outbreak of methanol poisoning in Azerbaijan revealed many shortcomings and weaknesses in the country's public health system. Late or erroneous diagnosis, lack of knowledge and clinical experience in the diagnosis and management of poisoned patients, difficulties with laboratory and diagnostic confirmation of the diagnosis, restrictions in the treatment of patients, relating to the lack of an effective antidote (fomepizole) resulted in high mortality. Considering the almost complete absence of methanol poisoning in Azerbaijan over the previous decade, the question of the source of the methanol is raised. Until a few years ago, the only methanol plant in the Caucasus was opened in Azerbaijan with a production capacity of more than 400 thousand tons per year. The plant stores more than 48 thousand metric tons of finished product, and should be investigated for possible leakage to the illegal market.

Molecular optimization of phytochemicals into antidotes

Military personnel and indeed civilians living and working in dangerous places are prone to envenomation by snakes, insects, and other animals that inject toxins into their blood system and may at times be fatal. Besides envenomation, drug overdose and poison ingestion can occur at any time, either deliberately or accidentally, possibly ending in fatalities. To date, they have been little research done to design and discover antidotes despite their paramount relevance to society. In light of this reality, medicinal chemists, biochemists, and other scientists involved in the drug development and discovery pipeline have to give significant attention to the development of appropriate antidotes and antivenoms that will have a large extent of effectiveness against the overdosed drug or the poisons. The process may start from a library of phytocompounds, synthetic compounds, de novo compounds on the bench, or antivenom development from antibodies of appropriate animal models. It is therefore important for military research and development units to work hand in hand with the academia and the pharmaceutical industry so that antidotes and antivenoms can be developed faster and be readily available for fieldwork and for civilian hospitals at all times. The recent advances in technology in the pharmaceutical industry have provided an easier and cheaper route to design and discover new medicines through computer-aided drug discovery (CAAD). This chapter briefly discusses a basic outline of how drug-like antidotes can be developed in parallel comparison to drug development with COVID-19 drug development as a model example. © 2021 Elsevier Inc. All rights reserved.

Pharmacologic and Clinical Considerations of Nalmefene, a Long Duration Opioid Antagonist, in Opioid Overdose

Opioid use disorder is a well-established and growing problem in the United States. It is responsible for both psychosocial and physical damage to the affected individuals with a significant mortality rate. Given both the medical and non-medical consequences of this epidemic, it is important to understand the current treatments and approaches to opioid use disorder and acute opioid overdose. Naloxone is a competitive mu-opioid receptor antagonist that is used for the reversal of opioid intoxication. When given intravenously, naloxone has an onset of action of approximately 2 min with a duration of action of 60–90 min. Related to its empirical dosing and short duration of action, frequent monitoring of the patient is required so that the effects of opioid toxicity, namely respiratory depression, do not return to wreak havoc. Nalmefene is a pure opioid antagonist structurally similar to naltrexone that can serve as an alternative antidote for reversing respiratory depression associated with acute opioid overdose. Nalmefene is also known as 6-methylene naltrexone. Its main features of interest are its prolonged duration of action that surpasses most opioids and its ability to serve as an antidote for acute opioid overdose. This can be pivotal in reducing healthcare costs, increasing patient satisfaction, and redistributing the time that healthcare staff spend monitoring opioid overdose patients given naloxone.

Cyanorona-20: The first potent anti-SARS-CoV-2 agent.

Explicit hindrance and blockade of the viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is considered one of the most promising and efficient approaches for developing highly potent remedies for COVID-19. However, almost all of the reported viral RdRp inhibitors (either repurposed or new antiviral drugs) lack specific selectivity against the novel coronaviral RdRp and still at a beginning phase of advancement. Herein, I discovered and introduce a new pyrazine derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 RdRp inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively). This promising selective specific anti-COVID-19 compound is also deemed to be the first distinctive derivative of favipiravir. Cyanorona-20, the unprecedented nucleoside/nucleotide analog, was designed, synthesized, characterized, computationally studied, and biologically evaluated for its anti-COVID-19 actions (through a precise in vitro anti-COVID-19 assay). The results of the biological assay displayed that cyanorona-20 surprisingly exhibited very high and largely significant anti-COVID-19 activities (anti-SARS-CoV-2 EC50 = 0.45 µM), and, in addition, it could be also a very promising guide and lead compound for the design and synthesis of new anti-SARS-CoV-2 and anti-COVID-19 agents through structural modifications and further computational studies. Further appraisal for the improvement of cyanorona-20 medication is a prerequisite requirement in the coming days. In a word, the ascent of the second member (cyanorona-20 "Corona Antidote") of the novel and promising class of anti-COVID-19 pyrazine derivatives would drastically make a medical uprising in the pharmacotherapeutic treatment regimens and protocols of the recently-emerged SARS-CoV-2 infection and its accompanying COVID-19.